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Kun Li,
Wei Su,
Man Li,
Chang-Jie Chen, Yong-Yu Li,
Lin-Yun Lai,
Ming-Min Zhang,
Shao-Jun Liu,
Jakub Fichna,
Ai Peng,
Chuan-Ming Hao,
Yong Gu,
Shan-Yan Lin
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ABSTRACT: The role of metabolic acidosis in the progression of chronic kidney disease (CKD) remains unclear. The aim of the present study was to investigate the direct effects of acid loading on the proliferation of rat glomerular mesangial cells (GMCs) in vitro and the possible role of sodium-hydrogen ion exchanger isoform 1 (NHE1). Rat GMCs were treated with acidic medium as acid loading. Growth and proliferation of GMCs was studied by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay, thymidine ((3)H-TdR) incorporation, and flow cytometry. NHE1 protein expression and activity were quantified by Western blot and dual wavelength epifluorescent illumination with 2',7'-bis-(2-carboxyethyl)-5(6)-carboxyfluorescein, respectively. 5-(N,N-dimethyl) amiloride hydrochloride (DMA), a specific inhibitor of NHE1, was used to investigate the possible involvement of NHE1 in the proliferation of GMCs. The MTT assay, (3)H-TdR incorporation, and cell cycle distribution analysis indicated that acid loading stimulated the proliferation of GMCs. Acid loading increased NHE1 activity, but had no effects on NHE1 expression at the protein level. The effects of acid loading on the proliferation of GMCs were inhibited by DMA. Acid loading induced GMC proliferation through NHE1-dependent pathways. Our findings may contribute to the understanding of metabolic acidosis in the progression of CKD.
Archiv für Experimentelle Pathologie und Pharmakologie 04/2013; · 2.65 Impact Factor
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ABSTRACT: OBJECTIVES: The anti-inflammatory effects of O-1602 and cannabidiol (CBD), the ligands of G protein-coupled receptor 55 (GPR55), on experimental acute pancreatitis (AP) were investigated. METHODS: Acute pancreatitis was induced in C57BL mice by intraperitoneal injection of 50 μg/kg cerulein hourly, with a total of 6 times. Drugs (O-1602, 10 mg/kg, or CBD, 0.5 mg/kg) were given by intraperitoneal injection 2 times at 30 minutes before the first injection and immediately before the fifth cerulein injection. At 3 hours after the last injection, the blood, the lungs, and the pancreas were harvested for the pancreatic enzyme activity, myeloperoxidase activity, and pro-inflammatory cytokines measurement; and the expressions of GPR55 mRNA and protein in the pancreas were detected. RESULTS: Cannabidiol or O-1602 treatment significantly improved the pathological changes of mice with AP and decreased the enzyme activities, IL-6 and tumor necrosis factor α levels, and the myeloperoxidase activities in plasma and in the organ tissues. G protein-coupled receptor 55 mRNA and protein expressed in the pancreatic tissue, and the expressions were decreased in the mice with AP, and either CBD or O-1602 attenuated these changes to a certain extent. CONCLUSION: Cannabidiol and O-1602 showed anti-inflammatory effects in mice with AP and improved the expression of GPR55 in the pancreatic tissue as well.
Pancreas 07/2012; · 2.39 Impact Factor
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ABSTRACT: Acute pancreatitis (AP), especially severe acute pancreatitis often causes extra-pancreatic complications, such as acute gastrointestinal mucosal lesion (AGML) which is accompanied by a considerably high mortality, yet the pathogenesis of AP-induced AGML is still not fully understood. In this report, we investigated the alterations of serum components and gastric endocrine and exocrine functions in rats with experimental acute pancreatitis, and studied the possible contributions of these alterations in the pathogenesis of AGML. In addition, we explored the intervention effects of cannabinoid receptor agonist HU210 and antagonist AM251 on isolated and serum-perfused rat stomach. Our results showed that the AGML occurred after 5 h of AP replication, and the body homeostasis was disturbed in AP rat, with increased levels of pancreatic enzymes, lipopolysaccharide (LPS), proinflammtory cytokines and chemokines in the blood, and an imbalance of the gastric secretion function. Perfusing the isolated rat stomach with the AP rat serum caused morphological changes in the stomach, accompanied with a significant increment of pepsin and [H(+)] release, and increased gastrin and decreased somatostatin secretion. HU210 reversed the AP-serum-induced rat pathological alterations, including the reversal of transformation of the gastric morphology to certain degree. The results from this study prove that the inflammatory responses and the imbalance of the gastric secretion during the development of AP are responsible for the pathogenesis of AGML, and suggest the therapeutic potential of HU210 for AGML associated with acute pancreatitis.
PLoS ONE 01/2012; 7(12):e52921. · 4.09 Impact Factor
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ABSTRACT: Inflammatory bowel disease (IBD) includes ulcerative colitis and Crohn's disease which is characterized by the recurrent intestinal inflammation and overactive immune responses. The signaling pathways of p38 mitogen-activated protein kinase (MAPK) play an important role in bowel inflammation. The inhibition of p38 MAPK can effectively suppress the expression of inflammatory mediators. However, due to the obvious preclinical and clinical side effects, p38 inhibitors are unacceptable in safety profiles and cannot be applied in the treatment of IBD. MAPK-activated protein kinase 2 (MK2), as the direct substrate of p38α and p38β, is a multifunctional signaling protein in the progression of inflammation and several lines of evidence demonstrate that the inhibition of MK2 may produce the same beneficial effect as the inhibition of p38 MAPK. Hence, MK2 is likely to be a potential drug target for the treatment of IBD.
Journal of Digestive Diseases 10/2011; 12(5):327-32. · 1.59 Impact Factor
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ABSTRACT: Melatonin is a hormone with endocrine, paracrine and autocrine actions. It is involved in the regulation of multiple functions, including the control of the gastrointestinal (GI) system under physiological and pathophysiological conditions. Since the gut contains at least 400 times more melatonin than the pineal gland, a review of the functional importance of melatonin in the gut seems useful, especially in the context of recent clinical trials. Melatonin exerts its physiological effects through specific membrane receptors, named melatonin-1 receptor (MT1), MT2 and MT3. These receptors can be found in the gut and their involvement in the regulation of GI motility, inflammation and pain has been reported in numerous basic and clinical studies. Stable levels of melatonin in the lower gut that are unchanged following a pinealectomy suggest local synthesis and, furthermore, implicate physiological importance of endogenous melatonin in the GI tract. Presently, only a small number of human studies report possible beneficial and also possible harmful effects of melatonin in case reports and clinical trials. These human studies include patients with lower GI diseases, especially patients with irritable bowel syndrome, inflammatory bowel disease and colorectal cancer. In this review, we summarize the presently available information on melatonin effects in the lower gut and discuss available in vitro and in vivo data. We furthermore aim to evaluate whether melatonin may be useful in future treatment of symptoms or diseases involving the lower gut.
World Journal of Gastroenterology 09/2011; 17(34):3888-98. · 2.47 Impact Factor
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ABSTRACT: The objective of this study was to investigate the function of heat shock protein 60 (HSP60) on pancreatic tissues by applying HSP60 small interfering RNA (siRNA) to reduce HSP60 expression. Rat pancreas was isolated and pancreatic tissue snips were prepared, cultured, and stimulated with low and high concentrations of cerulein (10(-11) and 10(-5) mol/L) or lipopolysaccharide (LPS, 10 and 20 μg/mL). Before the stimulation and 1 and 4 h after the stimulation, the viability and the level of trypsinogen activation peptide (TAP) in the tissue fragments were determined and the levels of tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6) in the culture supernatants were measured. Real-time PCR and Western blotting were used to evaluate the HSP60 mRNA and protein expression. After the administration of siRNA to inhibit HSP60 expression in the isolated tissues, these injury parameters were measured and compared. The pancreatic tissues in the control (mock-interfering) group showed a decreased viability to varying degrees after being stimulated with cerulein or LPS, and the levels of TAP, TNF-α, and IL-6 increased significantly (p < 0.05) in the tissues and/or in the culture supernatant. The expressions of HSP60 mRNA and protein were raised moderately after stimulating 1 h with low concentrations of cerulein or LPS, but decreased with high concentrations of the toxicants. In particular, the expression of HSP60 protein was reduced significantly (p < 0.05) when the tissues were stimulated by the two toxicants for 4 h. In contrast, the tissue fragments in which HSP60 siRNA was applied showed much lower tissue viability (p < 0.01) and higher levels of TNF-a, IL-6, and TAP (p < 0.01) in the tissues or culture supernatant after stimulating with the toxicants at the same dose and for the same time duration as compared with those of the control groups (p < 0.05). The results indicated that both cerulein and LPS can induce injuries on isolated pancreatic tissues, but the induction effects are dependent on the duration of the stimulation and on the concentrations of the toxicants. HSP60 siRNA reduces HSP60 expression and worsens the cerulein- or LPS-induced injuries on isolated pancreatic tissues, suggesting that HSP60 has a protective effect on pancreatic tissues against these toxicants.
Cell Stress and Chaperones 11/2010; 15(6):965-75. · 3.01 Impact Factor
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ABSTRACT: Many etiological factors are involved in the pathogenesis of acute pancreatitis. The pathogenesis of acute pancreatitis has been attributed to such causes as trypsin autodigestion, pancreatic microcirculation malfunction, the calcium overload in pancreatic acinar cells, oxygen free radical injury, cytokine injury, and has been treated in detail in numerous reviews. More recently, heat shock proteins (HSP), particularly heat shock protein 60 (HSP60), have receive increasing attention as another possible factor in the pathogenesis and development of acute pancreatitis. This brief review aims to: (i) outline our current understanding of HSP and their role in pancreatitis; (ii) discuss the available evidences that suggest HSP's interplay between pancreas tissues and etiological agents; (iii) delineate the functional mechanisms of HSP proposed by different research groups, and offer new thinking in preventing and treating acute pancreatitis in general.
Journal of Digestive Diseases 10/2010; 11(5):277-83. · 1.59 Impact Factor
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ABSTRACT: Acute pancreatitis (AP) is an inflammatory process in which cytokines and chemokines are involved. After onset, extrapancreatic stimuli can induce the expression of cytokines in pancreatic acinar cells, thereby amplifying this inflammatory loop. To further determine the role and mechanism of irritating agents in the pathogenesis of AP, rat pancreatic tissues were stimulated with ascitic fluid (APa) and serum (APs) from rats with AP or with lipopolysaccharide (LPS). In addition, the alteration of heat shock protein 60 (HSP60) expression was evaluated. Rat pancreas was removed and meticulously snipped to fragments. The snips were cultured for up to 48 h. During this period, the tissue viability as well as amylase and TNF-alpha levels in the supernatant and the HSP60 expression in the pancreatic tissue before and after stimulation by APa, APs, and LPS were assayed time-dependently. At different time-points during the culture, the viability and the amylase activity in the pancreatic tissue remained largely stable. After stimulation with APa, APs, or LPS for 1 h, the pancreatic tissues showed some damage, and this was followed by a sharp decrease in the viability accompanied by increased levels of amylase and TNF-alpha in the culture medium 2 or 4 h after stimulation (p < 0.05). In contrast, both the HSP60 mRNA and protein levels had a relatively high expression in the freshly prepared tissue fragments (0 h). As the culturing period was extended, the expression of HSP60 mRNA decreased only slightly; at the same time, the HSP60 protein levels decreased over a prolonged culture time, significantly so from 12 through 48 h (p < 0.05). After stimulation with APs, APa, or LPS, both the expression of HSP60 mRNA and protein in the tissue fragments increased slightly at 1 h and decreased significantly thereafter at 2 and 4 h (p < 0.05). APa, APs, or LPS induce injuries on isolated pancreatic tissues, accompanied by an altered HSP60 expression pattern in a time-dependent manner.
Cell Stress and Chaperones 02/2010; 15(5):583-91. · 3.01 Impact Factor
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ABSTRACT: The objective of this study was to investigate the role of MAPKAP kinase 2 (MK2) and heat shock protein (HSP) HSP60 in the pathogenesis of a new model of severe acute pancreatitis (AP). MK2 plays a significant role in the regulation of cytokines. It has been shown that induction and expression of several HSPs can protect against experimental pancreatitis. Interplay between both systems seems of high interest. Mice with a homozygous deletion of the MK2 gene were used. Severe AP was induced by combined intraperitoneal injections of cerulein with lipopolysaccharide (LPS). Severity of AP was assessed by biochemical markers and histology. The serum IL-6 and lung myeloperoxidase (MPO) levels were determined for assessing the extent of systemic inflammatory response. Expression of HSP25, HSP60, HSP70, and HSP90 was analyzed by Western blotting. Repeated injections of cerulein alone or cerulein plus LPS (Cer+LPS) resulted in local inflammatory responses in the pancreas and corresponding systemic inflammatory changes with pronounced severity in the Cer+LPS group. Compared with the C57Bl wild-type mice, the MK2-/- mice presented with significant milder pancreatitis and attenuated responses of serum amylase and trypsinogen activity. Furthermore, serum IL-6 was decreased as well as lung MPO activity. Injection of LPS alone displayed neither pancreatic inflammatory responses nor alterations of pancreatic enzyme activities but evidently elevated serum IL-6 levels and increased lung MPO activity. In contrast hereto, in the MK2-/- mice, these changes were much milder. Increased expression of HSP25 and HSP60 occurred after induction of AP. Especially, HSP60 was robustly elevated after Cer+LPS treatment, in both MK2-/- and wild-type mice. Thus the homozygous deletion of the MK2 gene ameliorates the severity of acute pancreatitis and accompanying systemic inflammatory reactions in a new model of severe acute pancreatitis. Our data support the hypothesis that MK2 participates in the multifactorial regulation of early inflammatory responses in AP, independently of the regulation of stress proteins like HSP25 and HSP60 and most likely due to its effect on cytokine regulation.
AJP Gastrointestinal and Liver Physiology 11/2009; 297(5):G981-9. · 3.43 Impact Factor
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ABSTRACT: To investigate the effects of serum and ascitic fluid from rats with acute pancreatitis (AP) on cellular free calcium concentration ([Ca(2+)]i) of isolated rat pancreatic acinar cells, and the intervention of pyrrolidine dithiocarbamate (PDTC) and tetrandrine (Tet) to cellular calcium overload in AP.
AP was induced in Sprague-Dawley rats with a retrograde pancreatic duct injection of 3% sodium deoxycholate, and confirmed by histopathological examination and amylase activity assay. The rat serum and ascitic fluid were collected at 1, 5 and 10 h after AP induction, and used as irritants on isolated rat pancreatic acinar cells. The effects on intracellular [Ca(2+)]i, and cell viability were examined. Then, the antagonistic effects of different concentrations of PDTC and Tet were assessed.
The irritation with AP serum and ascitic fluid reduced the survival rate of the isolated rat pancreatic acinar cells and increased the cellular [Ca(2+)]i significantly (P < 0.05). As AP induction course prolonged, the stimulation effect of the AP serum and ascitic fluid intensified. In the pretreated acinar cells with PDTC or Tet, the decreased cell vitality reverted. The elevation of [Ca(2+)]i in the acinar cells significantly ameliorated (significant, P < 0.05; very significant, P < 0.01).
The serum and ascitic fluid from AP rats drastically elevate the [Ca(2+)]i in isolated pancreatic acinar cells and decrease cell vitality, while the pretreatment of cells with PDTC and Tet offsets the calcium overload irritated by the AP serum and ascitic fluid and protects these isolated acinar cells.
Journal of Gastroenterology and Hepatology 01/2009; 24(1):155-65. · 2.87 Impact Factor
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ABSTRACT: The expression of heat-shock protein 60 (also known as chaperonin 60, Cpn60) in experimental acute pancreatitis (AP) is considered to play an active role in the prevention of abnormal enzyme accumulation and activation in pancreatic acinar cells. However, there are controversial results in the literature regarding the relationship between the abnormality of Cpn60 expression and AP onset and development. The purpose of this study was to investigate the alternations of Cpn60 expression and the relationship between the abnormal expression of Cpn60 and AP progression in rat severe acute pancreatitis (SAP) models. In this report, we induced SAP in Sprague-Dawley (SD) rats by reverse injection of sodium deoxycholate into the pancreatic duct, and examined the dynamic changes of Cpn60 expression in pancreatic tissues from different time points and at different levels with techniques of real-time PCR, western blotting, and immunohistochemistry. At 1 h after SAP induction, the expression of Cpn60 mRNA in the AP pancreatic tissues was higher than those in the sham-operation group and normal control group, but decreased sharply as the time period was extended, and there was a significant difference between 1 h and 10 h after SAP induction (p < 0.05). In the AP process, Cpn60 protein expression showed transient elevation as well, and the increased protein expression occurred predominantly in affected, but not totally destroyed, pancreatic acinar cells. As AP progressed, the pancreatic tissues were seriously damaged, leading to a decreased overall Cpn60 protein expression. Our results show a complex pattern of Cpn60 expression in pancreatic tissues of SAP rats, and the causality between the damage of pancreatic tissues and the decrease of Cpn60 level needs to be investigated further.
Cell Stress and Chaperones 09/2008; 14(2):199-206. · 3.01 Impact Factor
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ABSTRACT: The aim was to investigate alterations of intestinal motility in models of acute pancreatitis and to investigate the effects of the Chinese herbal preparation Qing Yi Tang (QYT) on these alterations. Upper gastrointestinal transit was evaluated in mice following induction of mild acute pancreatitis (MAP) using caerulein. Myoelectrical activity was recorded in rats after induction of severe acute pancreatitis (SAP) using sodium deoxycholate (SDOC). The contractility of jejunum segments was evaluated in the presence of SDOC, lipopolysaccharide (LPS) and trypsin. QYT accelerated the transit in MAP mice in a concentration dependent manner. Slow wave activity of smooth muscle in rat stomach and jejunum remained unchanged following SAP, but the spiking activity was significantly decreased, with bursts of 7.2 +/- 2.6/10 min compared with 47.9 +/- 13.2/10 min without SAP (p < 0.01). QYT reversed this decrease. Additionally, the amplitudes of slow waves and spikes were enhanced by QYT in SAP rats. The tension and amplitude of spontaneous contractile activity was reduced by SDOC and LPS and increased by trypsin. Gastrointestinal (GI) transit is altered by SAP but not by MAP. The Chinese herbal preparation QYT improves disturbed motility in AP by stimulating myoelectrical activity and accelerating GI transit.
Phytotherapy Research 05/2007; 21(4):324-31. · 2.09 Impact Factor
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ABSTRACT: To investigate the effect of Tetrandrine (Tet) on LPS-induced NF-kappaB activation and cell injury in pancreatic acinar cells and to explore the mechanism of Tetrandrine preventing LPS-induced acinar cell injury.
Male rat pancreatic acinar cells were isolated by collagenase digestion, then exposed to LPS (10 mg/L), Tet (50 micromol/L, 100 micromol/L) or normal media. At different time point (30 min, 1 h, 4 h, 10 h) after treatment with the agents, cell viability was determined by MTT, the product and nuclear translocation of subunit p65 of NF-kappaB was visualized by immunofluorescence staining and nuclear protein was extracted to perform EMSA which was used to assay the NF-kappaB binding activity.
LPS induced cell damage directly in a time dependent manner and Tet attenuated LPS-induced cell damage (50 micromol/L, P < 0.05; 100 micromol/L, P < 0.01). NF-kappaB p65 immunofluorescence staining in cytoplasm increased and began showing its nuclear translocation within 30 min and the peak was shown at 1 h of LPS 10 mg/L treatment. NF-kappaB DNA binding activity showed the same alteration pattern as p65 immunofluorescence staining. In Tet group, the immunofluorescence staining in cytoplasm and nuclear translocation of NF-kappaB were inhibited significantly.
NF-kappaB activation is an important early event that may contribute to inflammatory responses and cell injury in pancreatic acinar cells. Tet possesses the protective effect on LPS-induced acinar cell injury by inhibiting NF-kappaB activation.
World Journal of Gastroenterology 08/2006; 12(26):4232-6. · 2.47 Impact Factor
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ABSTRACT: To evaluate the protective effect of tetrandrine (Tet) on lipopolysaccharide (LPS)-induced pancreatic acinar cell damage and to explore its mechanism.
SD male rat's pancreatic acinar cells were isolated by collagenase digestion and they were pre-treated with Tet (50 micromol/L and 100 micromol/L), then exposed to LPS (10 mg/L) or conventional culture medium respectively. At 0, 1, 4, 10 hours after treatment with the agents, cell viability was determined by methyl thiazolyl tetrazolium (MTT), and the supernatant supernate of cells was collected for determination of the content of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) and phospholipase A(2) (PLA(2)). Some cells were loaded with Fluo-3/AM, and the dynamic change in intracellular Ca(2+) ([Ca(2+)]i) in single pancreatic acinar cell was determined by laser scanning confocal microscopy.
Tet attenuated LPS-induced cell damage (P<0.05 and P<0.01) and inhibited the elevation of cytosolic free calcium of rat pancreatic acinar cells. In the supernatant, Tet pretreatment decreased the content of MDA and the activity of PLA(2) and increased the activity of SOD (all P<0.05).
Tet attenuates LPS-induced cell damage by blocking [Ca(2+)]i overload, inhibiting superoxide response, decreasing activity of pancreatic enzyme, thus it shows a protective effect on pancreatic acinar cells.
Zhongguo wei zhong bing ji jiu yi xue = Chinese critical care medicine = Zhongguo weizhongbing jijiuyixue 04/2006; 18(3):157-60.
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ABSTRACT: To investigate alterations of the pancreatic endocrine component in the early stage of acute necrotic pancreatitis (ANP) in rats.
Thirty-six Sprague-Dawley rats were randomly allocated to two groups: ANP group (n = 18) and sham-operated (control) group (n = 18). ANP was induced by retrograde injection of 4% sodium deoxycholate (40 mg/kg, 0.1 mL/min) into the biliopancreatic duct and the severity of pancreatitis induced was assessed by histopathological examination and level of plasma amylase. The pancreatic endocrine function was assessed by measuring the levels of plasma glucose and insulin and by measuring the insulin content in pancreatic beta cells by immunofluorescence and immunocytochemistry.
Five hours after operation, the pancreas of rats in the ANP group showed pathological changes with edema, hemorrhage, fatty necrosis, acinar destruction and leukocyte infiltration in the exocrine portion of the pancreas. Plasma amylase activity increased significantly (P < 0.01) and bloody ascites appeared in the abdominal cavity. Nevertheless the endocrine islets appeared normal and the beta cells contained intensive labeling of insulin. Levels of glucose and insulin in plasma increased significantly. In the ANP group, 5 h after operation the plasma level of glucose was 8.18 +/- 2.26 mmol/L vs 6.39 +/- 1.26 mmol/L, and of insulin was 23.27 +/- 3.50 MIU/L vs 18.40 +/- 3.98 MIU/L. In the control group, 5 h after operation the plasma level of glucose was 9.39 +/- 0.62 mmol/L vs 5.89 +/- 0.62 mmol/L, and of insulin was 26.28 +/- 4.77 MIU/L vs 12.89 +/- 2.05 MIU/L; there was no significant difference between these two groups (P > 0.05). After a bolus injection of glucose, however, a much higher level of insulin was found in the control group (35.30 +/- 5.05 MIU/L) than that in the ANP group (23.91 +/- 4.62 MIU/L, P < 0.05).
There may be an impaired ability of insulin release in response to glucose stimulation in the early stage of ANP, although the morphology of the pancreatic endocrine component remains intact.
Chinese Journal of Digestive Diseases 02/2006; 7(3):164-9.
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ABSTRACT: To investigate the changes of chaperonin60 (Cpn60) and pancreatic enzymes in pancreatic acinar cells, and to explore their roles in the development of experimental diabetes and acute pancreatitis (AP).
Two different pathological models were replicated in Sprague-Dawley rats: streptozotocin-induced diabetes and sodium deoxycholate-induced AP. The contents of Cpn60 and pancreatic enzymes in different compartments of the acinar cells were measured by quantitative immunocytochemistry.
The levels of Cpn60 significantly increased in diabetes, but decreased in AP, especially in the zymogen granules of the pancreatic acinar cells. The elevation of Cpn60 was accompanied with the increased levels of pancreatic lipase and chymotrypsinogen in diabetes. However, a decreased Cpn60 level was accompanied by high levels of lipase and chymotrypsinogen in AP. The amylase level was markedly reduced in both the pathological conditions.
The equilibrium between Cpn60 and pancreatic enzymes in the acinar cells breaks in AP, and Cpn60 content decreases, suggesting an insufficient chaperone capacity. This may promote the aggregation and autoactivation of the premature enzymes in the pancreatic acinar cells and play roles in the development of AP.
World Journal of Gastroenterology 01/2006; 11(46):7359-63. · 2.47 Impact Factor
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Zhongguo wei zhong bing ji jiu yi xue = Chinese critical care medicine = Zhongguo weizhongbing jijiuyixue 01/2005; 16(12):764-7.
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ABSTRACT: To study the change of intracellular calcium-magnesium ATPase (Ca(2+)-Mg(2+)-ATPase) activity in pancreas, liver and kidney tissues of rats with acute pancreatitis (AP), and to investigate the effects of Qingyitang (QYT) (Decoction for clearing the pancreas) and tetrandrine (Tet) and vitamin E (VitE) on the activity of Ca(2+)-Mg(2+)-ATPase.
One hundred and five Sprague-Dawley rats were randomly divided into: normal control group, AP group, treatment group with QYT (1 ml/100 g) or Tet (0.4 ml/100 g) or VitE (100 mg/kg). AP model was prepared by a retrograde injection of sodium taurocholate into the pancreatic duct. Tissues of pancreas, liver and kidney of the animals were taken at 1 h, 5 h, 10 h respectively after AP induction, and the activity of Ca(2+)-Mg(2+)-ATPase was studied using enzyme-histochemistry staining. Meanwhile, the expression of Ca(2+)-Mg(2+)-ATPase of the tissues was studied by RT-PCR.
The results showed that the positive rate of Ca(2+)-Mg(2+)-ATPase in AP group (8.3%, 25%, 29.2%) was lower than that in normal control group (100%) in all tissues (P<0.01), the positive rate of Ca(2+)-Mg(2+)-ATPase in treatment group with QYT (58.3%, 83.3%, 83.3%), Tet (50.0%, 70.8%, 75.0%) and VitE (54.2%, 75.0%, 79.2%) was higher than that in AP group (8.3%, 25.0%, 29.2%) in all tissues (P<0.01). RT-PCR results demonstrated that in treatment groups Ca(2+)-Mg(2+)-ATPase gene expression in pancreas tissue was higher than that in AP group at the observing time points, and the expression at 5 h was higher than that at 1 h. The expression of Ca(2+)-Mg(2+)-ATPase in liver tissue was positive, but without significant difference between different groups.
The activity and expression of intracellular Ca(2+)-Mg(2+)-ATPase decreased in rats with AP, suggesting that Ca(2+)-Mg(2+)-ATPase may contribute to the occurrence and development of cellular calcium overload in AP. QYT, Tet and VitE can increase the activity and expression of Ca(2+)-Mg(2+)-ATPase and may relieve intracellular calcium overload to protect the tissue and cells from injuries.
World Journal of Gastroenterology 01/2004; 10(1):100-4. · 2.47 Impact Factor
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ABSTRACT: To investigate the therapeutic effect of Qingyi Decoction (QYD) and tetrandrine (Tet), used singly or combind, in treating miniature pigs with severe acute pancreatitis (SAP) and its mechanism.
Thirty-two Guizhou miniature pigs were made into SAP model by pancreatic duct retrograde injection of 5% sodium taurocholate. They were randomly divided into 4 groups: the control group, the QYD group, the Tet group and the combined treated group. The serum amylase activity and interleukin-1 and 6 (IL-1, IL-6) contents in serum from vena cava and portal vein were tested by biochemistry and radioimmunoassay (RIA). Serum emodin and plasma Tet levels were measured by high performance liquid chromatography (HPLC) 24, 48 and 72 hrs after treatment. And the pathological changes of pancreas, lung and liver were observed under microscope.
The mortality of SAP pigs was reduced significantly and the inflammatory injury of the organs was ameliorated obviously in all treated groups, and the increased amylase activity and IL-1, IL-6 levels was attenuated. The therapeutic effect was much more obvious, and the plasma Tet level at different time points were much higher in the combined treated group than those in the other two groups treated by single drug (P < 0.01).
Both QYD and Tet could treat effectively SAP through multiple pathways, combination of them reveals an elevation of serum drug concentration and shows a synergistic effect.
Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine / Zhongguo Zhong xi yi jie he xue hui, Zhongguo Zhong yi yan jiu yuan zhu ban 12/2003; 23(11):832-6.
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ABSTRACT: To investigate the role of phospholipase A(2) (PLA(2)) in injury of lung complicated by acute pancreatitis (AP) and the therapeutic effect of verapamil, furthermore to explore its possible mechanism.
Eighty-two Sprague-Dawley rats both male and female were divided into three groups. AP was induced by injecting 3% sodium deoxycholate (1 ml/kg) into the biliopancreatic duct except the rats of sham operation group. Ten minutes after operation, rats were injected intraperitoneally with saline or verapamil, respectively. At 4 hours and 8 hours after treatment, the volume of as cites and pulmonary coefficient were measured. The amylase activity and calcium concentration in plasma and PLA(2) in ascites and homogenate of lung were determined. The survival time and mortality of rats in different groups were recorded, and the pathomorphism of pancreas and lung was observed under microscope.
Verapamil reduced the mortality (P<0.05), and prolonged the survival time of rats with AP significantly (P<0.05), attenuated ascites volume, amylase activity and hypocalcemia in plasma, PLA(2) activity in ascites and lung homogenate, and ameliorated the inflammatory injury of pancreas and lung.
The results suggest that PLA(2) plays a role in the injury of lung complicated by AP and verapamil possesses a therapeutic effect on the AP induced by sodium deoxycholate in rats, in which the mechanism might be due to inhibit PLA(2) activity by blocking calcium channel to ameliorate the damage of pancreas and lung which is induced by the overload of Ca(2+).
Zhongguo wei zhong bing ji jiu yi xue = Chinese critical care medicine = Zhongguo weizhongbing jijiuyixue 08/2003; 15(7):418-21.
