[Show abstract][Hide abstract] ABSTRACT: Objective:
To determine the roles of mitochondrial apoptosis and energy metabolism in hepatocytes during the pathogenic process of acute renal failure (ALF) by assessing disease-related differential activities of several key mitochondrial enzymes, including citrate synthase (CS), carnitine palmitoyltransferase-1 (CPT-1) and cytochrome c oxidase (COX).
Thirty-two male Sprague Dawley rats were given D-galactosamine followed by and lipopolysaccharide (LPS) to induce acute liver failure and sacrificed after 4 (4 h group), 8 (8 h group) 12 (12 h group) and 24 hours (24 h group) of treatment. Eight unmodeled rats served as controls. Effects related to apoptosis were evaluated by pathological analysis of hepatic tissues and TUNEL staining. Ultrastructural changes in mitochondria were assessed by electron microscopy. The activity and expression of CS, CPT-1 and COX were measured.
Hepatocyte apoptosis was present in the 4 h treatment group and was increased obviously in the 8 h treatment group. Hepatocyte necrosis was first observed in the 12 h treatment group and was significantly higher in the 24 h treatment group, with inflammatory cell invasion. Ultrastructural changes in mitochondria were present in the 4 h treatment group, and the 24 h treatment group showed mitochondria with completely destroyed outer membranes, which resulted in mitochondrial collapse. Activity and protein expression of CS, CPT-1 and COX were increased in the 4 h group (vs. controls), were at their peak in the 8 h group (CS:t =1.481, P less than 0.01; CPT-1:t =2.619, P less than 0.05; COX:t =1.014, P less than 0.01) and showed a decreasing trend in the 12 h group. In addition, the activities of CS, CPT-1 and COX were enhanced at the stage of hepatocyte apoptosis, suggesting that these enzymes were involved in the initiation and development of ALF.
Energy metabolism plays an important role in hepatocyte apoptosis during ALF.
No preview · Article · May 2014 · Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology
[Show abstract][Hide abstract] ABSTRACT: Objective:
To explore the effects of compound nutrients on liver rehabilitation and regeneration in rats with CCl4;-induced liver cirrhosis.
The rat cirrhotic models were prepared by injecting intraperitoneally the mixture of CCl4; (40%) and oil (60%) by 2 mL/kg body weight twice a week for 12 weeks. The nutrition treatment group was treated with compound nutrients and the spontaneous recovery group was not treated with nutrients after stopping CCl4; injection. Then liver tissues and blood samples were harvested to detect the expressions of augmenter of liver regeneration (ALR) and proliferating cell nuclear antigen (PCNA) by immunohistochemistry, the level of hepatocyte growth factor (HGF) by ELISA, the levels of albumin (ALB), alanine aminotransferase (ALT), total bilirubin (TBIL), glucose, triglyceride (TG) and cholesterol (CHOL) by automatic biochemical analyzer, and the levels of amino acids in blood plasma by mass spectrometry.
The expressions of ALR and PCNA were higher in nutrition treatment group than in spontaneous recovery group. The level of HGF in serum was higher in nutrition treatment group than in spontaneous recovery group (98.92 ± 2.42 vs 60.99 ± 27.63, t = 3.349, P = 0.020). The levels of ALT (60.18 ± 6.39 vs 84.6 ± 17.91, t = 3.146, P = 0.019) and TBIL (2.08 ± 0.46 vs 6.97 ± 2.58, t = 4.56, P = 0.001) were lower in nutrition treatment group than in spontaneous recovery group. The level of ALB was higher in nutrition treatment group than in spontaneous recovery group (33.15 ± 1.36 vs 24.62 ± 2.48, t = 7.39, P=0.000). The level of branched chain amino acids (BCAA) in blood plasma was higher in nutrition treatment group than in spontaneous recovery group (381.53 ± 35.86 vs 283.05 ± 79.14, t = 2.78, P = 0.02).
Compound nutrients can be good for liver rehabilitation and regeneration in CCl4;-induced cirrhotic rat model, and the liver regeneration may relate to high BCAA level in blood plasma.
No preview · Article · Dec 2013 · Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology
[Show abstract][Hide abstract] ABSTRACT: To investigate the correlation between procoagulation factors and anti-coagulation factors synthesized by the liver, and the correlation between fibrin degradation products (FDP) and D-dimer (D-D) concentration and coagulation proteins synthesized by extra-hepatic tissues, in different liver diseases; to explore the relationship between coagulation and bleeding in hepatic diseases.
Chronic hepatitis B (CHB) patients, CHB-related liver cirrhosis patients, CHB-related liver failure patients and healthy (normal) controls were selected for study and provided blood samples for analysis. The activity of coagulation factors (F) II, V, VII, VIII, IX, X, XI, and XII was detected using the one-stage clotting method. Coagulogram analysis, including activated partial thromboplastia time (APTT), thrombin time (TT), and prothrombin time (PT), was conducted by the solidification method. Antithrombin III (AT-III) and protein C (PC) activities were measured by chromogenic substrate assay. FDP concentration was detected using immunoturbidimetry. Tissue factor pathway inhibitor (TFPI), thrombomodulin (TM), von Willebrand factor (vWF), and tissue factor (TF) concentrations were measured by enzyme-linked immunosorbent assay (ELISA).
With the exception of FVIII, coagulation factors and anticoagulant proteins synthesized by the liver were decreased and the coagulogram was extended for all patients. Likewise, the FDP and D-D concentrations were increased in blood. CHB patients, however, presented with increased levels of FVIII, TFPI, TM, vWF, and TF. Pairwise comparison indicated statistical differences existed among CHB, CHB-realted liver cirrhosis, and liver failure patients: TFPI: 239.3+/-206.4, 315.0+/-258.6, and 319.5+/-298.1 -- higher than normal control: 104.0+/-87.1, F = 5.453, P less than 0.05; vWF: 70.3+/-29.5, 105.5+/-58.0, and 179.3+/-61.7 -- higher than normal control: 21.9+/-7.2, F = 20.104, P less than 0.05; TF: 85.9+/-85.7, 234.2+/-202.9, and 344.7+/-214.6 -- higher than normal control: 12.8+/-8.1, F = 8.619, P less than 0.05; FVIII: 157.2+/-53.4, 206.9+/-86.9, and 335.7+/-117.7 -- higher than normal control: 105.5+/-46.2, F = 13.418, P less than 0.05.
In parallel to the progression of liver diseases, procoagulation and anti-coagulation elements synthesized by the liver were reduced. In contrast, fibrinolysis activity was enhanced, which is expected to lead to an imbalance between blood clotting and anti-clotting factors. This may be an important cause for the bleeding that occurs in end-stage liver disease. Expressions of TFPI, TM, vWF, and TF significantly change in the early stage of liver diseases, as compared to normal (healthy) levels, and may represent a sensitive indicator of vascular injury.
No preview · Article · Mar 2012 · Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology
[Show abstract][Hide abstract] ABSTRACT: To observe the effects of neurotrophin 3(NT-3)on interdigestive migrating motor complex (MMC) in rats with D-galactosamine induced acute liver injury.
Twenty-four specific pathogen-free purebred rats were equally randomized into control and acute liver injury groups. The control group was injected with equal volume of normal saline via tail vein. Acute liver injury model of the rats was induced by D-galactosamine injection via the tail vein in the acute liver injury group. And the indexes of interdigestive MMC before and after NT-3 injection were recorded by a polygraph and analyzed in model group. The serum NT-3 concentration was assayed in the two groups.
There were no significant changes of gastrointestinal MMC cycle and jejunal phase I MMC after NT-3 injection. Compared with the acute liver injury rats before NT-3 injection , the antral phases I, III and IV MMC were significantly prolonged [(577.44 ± 248.60)s vs (343.58 ± 227.30) s, (80.94 ± 21.15) s vs (24.76 ± 7.41) s, (405.69 ± 131.34) s vs (191.67 ± 128.15) s, P < 0.05] and the phase II MMC was shortened [ (883.94 ± 488.50) s vs (1519.00 ± 831.14) s, P < 0.05] in the acute liver injury group. The duodenal phases I, III and IV MMC were significantly prolonged [ (557.63 ± 335.14) s vs (309.46 ± 220.22) s,(75.91 ± 15.75) s vs (31.15 ± 13.67) s, (423.38 ± 135.22) s vs (209.77 ± 123.83) s, P < 0.05] and MMC II phase was shortened [ (748.81 ± 579.69) s vs (1535.86 ± 930.50) s, P < 0.05] in the acute liver injury rats. In addition, the jejunal MMC III and MMC IV phase was significantly prolonged [ (86.58 ± 23.40) s vs (31.41 ± 16.09) s,(385.18 ± 110.02) s vs (220.59 ± 159.30) s, P < 0.05] and phase II MMC was shortened [ (876.89 ± 652.01) s vs (1870.89 ± 1010.35) s, P < 0.05 ] in the acute liver injury rats. The serum NT-3 level was significantly higher in model group than in control group.
NT-3 could enhance the gastrointestinal motility in acute liver injury rats.
No preview · Article · Sep 2010 · Nan fang yi ke da xue xue bao = Journal of Southern Medical University
[Show abstract][Hide abstract] ABSTRACT: To observe the changes and characteristics of interdigestive migrating motor complex (MMC) in rat models of acute liver failure.
30 rat models with acute liver failure were induced with D-galactosamine and another 30 normal rats were used as controls. The indexes of MMC recorded by multi-channel physiological recorder were compared.
No significant differences found between the two groups in antral and duodenal MMC cycles and frequencies of duodenal and jejunal MMC III phase. Compared with normal controls, the MMC II phase in the acute liver failure rats was significantly prolonged (t=-3.97, -3.85, P<0.05), the MMC III duration of antrum and duodenum (u=-4.99, t=4.66, P<0.05) was shorter and the MMC III frequency of antrum (u=-4.73, P<0.05) was faster. In addition, the MMC cycle and MMC III phase of jejunum were significantly prolonged (u=-1.63, t=-4.94, P<0.05) and the MMC III phase duration was significantly shorter in the acute liver failure rats (t=5.10, P<0.05).
Significantly prolonged MMC II phase characterized by migrating clustered contraction, shortened MMC III phase and extended jejunal MMC cycles were probably the major contributors to the gastrointestinal motility disorders in the rats with acute liver failure.
No preview · Article · Aug 2010 · Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology