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ABSTRACT: To study the effect of arctiin on mouse podocyte epithelial-mesenchymal transition (EMT) induced by advanced oxidation protein products (AOPP).
Mouse podocytes were stimulated by 200 µg/ml AOPP for 24 h in the presence of 50, 100, 200, and 400 µmol/L arctiin. The expressions of α-smooth muscle actin, Grp78 and CHOP were detected using Western blotting.
The expressions of α-SMA, Grp78 and CHOP were inhibited by arctiin, showing a dose-dependent effect within a given range of arctiin concentration.
AOPP causes endoplasmic reticulum stress to induce EMT of mouse podocytes, and arctiin can decrease EMT by alleviating the stress. This finding sheds light on a new scope of research of renal fibrosis.
Nan fang yi ke da xue xue bao = Journal of Southern Medical University 03/2012; 32(3):379-82.
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ABSTRACT: To detect the effect of connective tissue growth factor (CTGF) on podocalyxin expression in mouse potocytes exposed to high glucose in vitro and explore the possible pathway involved.
The expression vector carrying a small interfering RNA (siRNA) targeting CTGF was transfected into mouse podocytes cultured in the presence of 1 g/L glucose (normal control), 4.5 g/L glucose (high glucose group), 1 g/L glucose + 3.5 g/L mannitol (iso-osmolar control group). The changes in the protein expression levels of podocalyxin, CTGF and ERK1/2 in the cells in response to the treatments were investigated using Western blotting.
High glucose exposure for 24 and 48 h resulted in significantly decreased expression of podocalyxin and increased CTGF in the podocytes (P<0.05). Phosphorylation of ERK1/2 occurred as early as 30 min after the exposure, and the activation was maintained till 24 h. Transfection of the cells with siRNA targeting CTGF significantly inhibited these changes.
CTGF is an important mediator of high glucose-induced potocyte damage and decreases the protein level of podocalyxin by the ERK1/2 pathway. CTGF-specific siRNA can alleviate high glucose-induced podocyte injury, suggesting its potential value in treatment of diabetic nephropathy.
Nan fang yi ke da xue xue bao = Journal of Southern Medical University 05/2011; 31(5):839-43.
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ABSTRACT: To investigate the epidemiology, peritoneal dialysis (PD) related complications and survival outcomes of 236 patients with end-stage renal disease (ESRD) undergoing continuous ambulatory peritoneal dialysis (CAPD) in our center from January, 2004 to November, 2009.
The data including patient gender, age, time of PD initiation, addresses, types of medical reimbursement, primary diseases, modes of PD catheter placement surgery, types of PD catheter, PD-related complications, and time of drop out were retrospectively analyzed. PD catheter migration rate, peritonitis rate, drop out rate (DOR), length of the time of PD therapy (TOT), and survival rate were calculated and compared with those of patients in other PD centers.
The number of newly introduced patients increased gradually in the years from 2004 to 2009. The mean age of newly introduced patients was 47-/+16 years, and patients with age below 60 years accounted for 77.96%. Patients who paid for their own expenses accounted for 67.37% of all, and the rate of these patients decreased gradually. Similar to that in Asian-Pacific region, chronic glomerulonephritis was the most frequent cause of ESRD followed by diabetic nephropathy. The number of patients with chronic glomerulonephritis or obstructive nephropathy as the primary diseases was greater in this center than that reported in the Asian-Pacific region, accounting for 54.66% and 11.02% of all patients, respectively. In contrast, the patients with diabetic nephropathy or benign arteriolar renal sclerosis were less, accounting for 12.29% and 10.17% of all, respectively. PD catheter migration rate (8.05%) and peritonitis rate (1:44.22 patient-months) were both lower than those reported. The patient survival rates at 1, 2, 3 years were 83.65%, 51.59% and 29.81%, respectively, lower than those of other centers in the developed countries but higher than the mean levels in China. DOR decreased gradually to 11.56% in 2009, and TOT increased to 23.61 months.
The above characteristics of the patients are related to many factors, including the "PD first" principle, high prevalence of urinary calculosis in the primary source regions of most patients, preventive partial omentum resection in some patients, education and follow-up for patients, and increased expense cover by medical insurance.
Nan fang yi ke da xue xue bao = Journal of Southern Medical University 06/2010; 30(6):1395-7.
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ABSTRACT: To identify the clinical characteristics and risk factors of frequent peritoneal dialysis (PD)-related peritonitis.
A retrospective analysis was conducted in the peritonitis patients undergoing continuous ambulatory peritoneal dialysis (CAPD) in our hospital. Frequent PD-related peritonitis was defined by two or more onsets in one year, and the patients with only one onset served as the control group. The clinical and laboratory data of the two groups were compared and the risk factors of PD-related peritonitis analyzed.
Forty-four episodes of peritonitis were recorded in the 16 patients with frequent PD-related peritonitis, as compared to 53 episodes in the 45 control patients. Compared with those in the control group, the patients with frequent peritonitis had significantly higher blood pressure (P<or=0.05) but lower hemoglobulin (P<or=0.05) and plasma albumin (P<or=0.01), with higher rates of edema (P<or=0.01), gram-negative bacteria and fungal infection (P<or=0.05) and PD catheter removal (P<or=0.05). No significant differences were found between the two groups in age, mode of catheter placement surgery, intervals between PD initiation and peritonitis occurrence, inducing factors of peritonitis, incidence of dyspnea, serum creatinin, urea, calcium, mineral phosphorus, blood or dialysate leucocytes (P>0.05). Variables identified to be associated with an increased likelihood of frequent PD-related peritonitis included hemoglobulin<70 g/L (OR=0.135, P<or=0.01) and plasma albumin<30 g/L (OR=0.181, P<or=0.05).
Compared with the patients with only one annual occurrence of peritonitis, the patients with frequent PD-related peritonitis have severer malnutrition and water overload, which are probably correlated to the high rates of PD catheter removal and poor prognosis. Severe anemia and proteinemia are risk factors and also predictive factors of frequent PD-related peritonitis. Measures to ameliorate anemia and proteinemia and effective management of celiac endogenous infection may help prevent and control frequent PD-related peritonitis.
Nan fang yi ke da xue xue bao = Journal of Southern Medical University 04/2010; 30(4):855-8.
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ABSTRACT: To observe the effect of transfection with small interfering RNA (siRNA) targeting connective tissue growth factor (CTGF) on human tubular epithelial hypertrophy induced by high glucose.
HK-2 cells were cultured in DMEM/F12 medium containing 1 g/L glucose (normal control group), 4.5 g/L glucose (high glucose group), or 1 g/L glucose+3.5 g/L mannitol (iso-osmolar control group). The cells were transfected with pGenesil-1, pGenesil/neg, or pGenesil/siRNA-CTGF and then cultured in DMEM/F12 medium containing 4.5 g/L glucose as the high glucose+blank control group, high glucose+negative control group and high glucose+interference group, respectively. After cell culture for 24, 48 and 96 h, the cells were collected to detect the mRNA and protein levels of CTGF by real-time PCR and Western blotting, respectively. The proliferative activities of the cells were evaluated with MTT assay, and the total cellular protein contents were determined with Bradford method. Flow cytometry was employed to analyzed the cell cycle changes.
High-glucose significantly up-regulated the CTGF mRNA and protein levels in HK-2 cells. The cell proliferation was inhibited after high-glucose exposure with increased cell percentage in G1 phase and total cellular protein content suggesting cellular hypertrophy. Transfection with siRNA targeting CTGF significantly inhibited high glucose-induced up-regulation of CTGF mRNA and protein and promoted the cell proliferation, resulting also increased cells in S phase and lowered total cellular protein contents. CONCLUISON: CTGF is an important mediator of high glucose-induced tubular epithelial hypertrophy, and transfection with siRNA targeting CTGF can alleviate the hypertrophy, suggesting the potential value of CTGF-targeted treatment in the management of diabetic nephropathy.
Nan fang yi ke da xue xue bao = Journal of Southern Medical University 10/2009; 29(10):2002-6.
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ABSTRACT: To observe the effect of high glucose exposure on connective tissue growth factor (CTGF) expression in cultured human renal tubular epithelial cells and investigate the role of p38MAPK pathway in this process.
Human renal tubular epithelial cells (HKC) with and without SB203580 pretreatment were cultured in the presence of high glucose levels for 24, 48, 72, 96 h and 20 days. RT-PCR, immunohistochemical staining, indirect fluorescence staining and Western blotting were used to detect the changes in CTGF mRNA and protein expressions in the cells after the treatment.
Low levels of CTGF mRNA and protein were detected in cultured HKC cells, and after high glucose treatment, the mRNA expression increased gradually and reached the peak level at 48 h, then followed by gradual decrease till recovering the baseline level at 96 h. Prolonged high glucose treatment for 20 days resulted in persisted high CTGF mRNA expression twice the level in the control group. The expression level of CTGF protein also increased progressively as the treatment time then prolonged, and long-term (20 days) treatment increased the expression by 4 folds in comparison with the expression in the control cells. SB203580 significantly inhibited the increase in the expressions of CTGF mRNA and protein stimulated by high glucose treatment.
High glucose treatment can increase CTGF mRNA and protein expressions in cultured human renal tubular epithelial cells, suggesting that increased CTGF levels is a key event in the pathogenesis of renal tubulo-interstitial fibrosis in patients with diabetic nephropathy. p38MAPK pathway may also participate in this process.
Nan fang yi ke da xue xue bao = Journal of Southern Medical University 02/2009; 29(1):50-3.
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Xun Tang
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ABSTRACT: To elucidate the significance of the changes in serum tissue inhibitor of metalloproteinase-1(TIMP-1) in patients with chronic nephritis, and investigate the changes of TIMP-1 concentrations after losartan therapy.
Serum TIMP-1 concentrations were measured by enzyme-linked immunosorbent assay (ELISA) in 45 patients with chronic nephritis and 10 healthy volunteers respectively, and the relationship between serum TIMP-1 concentration and the degree of renal fibrosis was investigated. The changes of serum TIMP-1 concentrations in patients after losartan therapy were measured in comparison with those of patients without losartan therapy.
Serum TIMP-1 concentration in patients with chronic nephritis was significantly higher than that in healthy subjects, and tended to exacerbate the glomerulosclerosis and interstitial fibrosis. Losartan therapy could improve the patients' renal functions, decrease the levels of urine protein and serum TIMP-1.
Serum TIMP-1 concentration was in close correlation with the degree of renal fibrosis. Losartan therapy could decrease serum TIMP-1 levels, indicating that losartan may slow down the progression of renal fibrosis by regulating the activity of metalloproteinases.
Di 1 jun yi da xue xue bao = Academic journal of the first medical college of PLA 10/2003; 23(9):966-9.
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Xun Tang
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ABSTRACT: To investigate the therapeutic effect of ligustrazine on proliferative nephritis.
45 patients with mesangial cell proliferation were randomly divided into two groups according to age, clinical manifestations and the pathological lesions. Steroid, cyclophosphamide, losartan and dipyridamole were given to 20 patients in the control group. Ligustrazine with the dosage of 80 mg twice a day was given to 25 patients in the treatment group by intravenous perfusion besides the medicine used in the control group. The course of ligustrazine treatment lasted three weeks.
The proteinuria and hematuria were decreased significantly with the increases of urine volume, serum albumin and creatinine clearance after ligustrazine treatment. The improvement of serum albumin, proteinuria and hematuria in the treated group were significant compared with control group after treatment.
Ligustrazine is eutherapeutic in treating proliferative glomerulonephritis, with the less risk of hemorrhage, ligustrazine can be used for long-term treatment without special monitored.
Zhong yao cai = Zhongyaocai = Journal of Chinese medicinal materials 09/2003; 26(8):611-2.
