1.Study the hepatoprotective effect of panax notoginseng on CCl4 and PAR - intoxicated rat liver
Journal of Medical Research 2004;27(1):39-45
Two rat hepatic intoxication models by high doses CCl4 and PAR were used. The experimental results showed that the oral administration of Panax Notoginseng (aqueous extract) with the dose of 5g/kg body weight has significantly reduced the serum concentrations of SGOT and SGPT with 29.1% and 43.1% respectively in comparison with that of CCl4 - treated control . In PAR - intoxicated group, Panax Notoginseng with the dose of 5g/kg body weight resulted in a marked decrease of SGOT and SGPT serum concentration 97.0% and 75.5%, respectively, which were significantly different from that of group without Panax Notoginseng. The hepatoprotective effect of Panax Notoginseng with the dose of 5g/kg and Silymarin with the dose of 25mg/kg on both CCl4 and PAR hepatic-intoxication models is the same. In histopathological examinations, Panax Notoginseng has improved CCl4 and PAR induced hepatic injuries
Panax notoginseng
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Carbon Tetrachloride
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poisoning
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liver
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rats
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Animal Experimentation
6.Proteomic analysis of proliferation and apoptosis in carbon tetrachloride induced rat liver fibrosis.
Ying LIU ; Ping LIU ; Cheng-hai LIU ; Yi-yang HU ; Lie-ming XU ; Yong-ping MU ; Guang-li DU
Chinese Journal of Hepatology 2005;13(8):563-566
OBJECTIVETo study the proliferation and apoptosis in carbon tetrachloride induced rat liver fibrosis.
METHODSWistar rats were injected subcutaneously with 40% CCl4-olive oil twice weekly for 12 weeks. Liver tissues were obtained at the end of 4, 8, 12 and 16 weeks for histological examination, hydroxyproline (Hyp) assay and proteomic analysis. After two dimension electrophoresis (2-DE), the silver stained gels were analyzed with PDQUEST 2-DE. More than 30 differentially expressed proteins were identified by MALDI-TOF-MS.
RESULTSThe degree of collagen deposition and hydroxyproline content of the fibrotic livers increased continuously during the 12 weeks of CCl4 administration, peaked at the end of week 12 (P < 0.05) and declined significantly at week 16 (P < 0.05). Significant differences were observed in two parameters at each time point between the control and the model group. Meanwhile, dramatic change of hepatic proteome in the model group rats was also seen. Differentially expressed proteins identified by MALDI-TOF-MS were categorized as proliferation-related proteins/enzymes (proliferating cell nuclear antigen p120, p40 and cyclin F ubiquitin-conjugating enzyme 7 UBC7), and apoptosis-related proteins, mainly caspase-12 which was absent in the control rats.
CONCLUSIONProliferation and apoptosis related proteins are expressed dynamically in different stages of rat liver fibrosis induced by CCl4.
Animals ; Apoptosis ; Carbon Tetrachloride ; Carbon Tetrachloride Poisoning ; Caspase 12 ; metabolism ; Cell Proliferation ; Hydroxyproline ; metabolism ; Liver Cirrhosis, Experimental ; chemically induced ; metabolism ; Male ; Proteins ; metabolism ; Proteome ; metabolism ; Rats ; Rats, Wistar
7.Evaluation of the liver reserve using lidocaine test on experimental liver injuries in rats.
Zhen-xia WANG ; Rui-ming ZHANG ; Lü-nan YAN ; Wen-tao WANG ; Qian-bin JIA
Chinese Journal of Hepatology 2006;14(6):445-448
OBJECTIVESTo study the effectiveness of the lidocaine test in evaluating the liver reserve of rats with experimental liver injury in different phases.
METHODS40 healthy male Wistar rats were divided randomly into experimental and control groups. Rats of the experimental group received subcutaneous CCl4 in oil injection, and rats of the control group received saline injections. Monoethylglycinexylidide (MEGX) test, common hepatic function tests and histological examination of the livers were performed on all the rats.
RESULTSWith the development of the severity in liver injury, the concentrations of the serum MEGX in lidocaine test decreased gradually, which were consistent with liver histological changes. However, the results from the common liver function tests were all abnormal in the experimental group and were not consistent with the liver histological changes.
CONCLUSIONThe results obtained from the MEGX test are more agreeable to liver histological changes than those from common liver function tests. The results from the MEGX test can represent liver histological changes concisely.
Animals ; Carbon Tetrachloride ; Carbon Tetrachloride Poisoning ; Lidocaine ; analogs & derivatives ; Liver ; pathology ; physiopathology ; Liver Cirrhosis, Experimental ; chemically induced ; pathology ; physiopathology ; Liver Function Tests ; Male ; Random Allocation ; Rats ; Rats, Wistar
8.The effect of Fuzheng Huayu Decoction on the hepatic proteome during the formation and resolution of rat liver fibrosis.
Ying LIU ; Ping LIU ; Lei WANG
Chinese Journal of Hepatology 2006;14(6):422-425
OBJECTIVETo investigate the dynamic changes of the hepatic proteome during the formation and resolution of rat liver fibrosis induced by carbon tetrachloride and the effect of Fuzheng Huayu Decoction on it.
METHODSLiver fibrosis in Wistar rats was induced by subcutaneous injection of 40% CCl4 in olive oil while the rats in the treatment group received Fuzheng Huayu Decoction. Pathological examination, hydroxyproline content determination and protein extraction of the rats livers were performed at four time points, i.e. at the end of 4, 8, 12 and 16 weeks. After 2-dimensional electrophoresis (2-DE), the gels were analyzed using the PDQUEST 2-DE image analysis software and differentially expressed proteins were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS).
RESULTS(1) The 2-DE examination showed that the model group-specific proteins and differentially expressed proteins presented started at 4 weeks and reached their peaks at 12 weeks, and this was conformed by MALD-TOF-MS identification. (2) In addition, 18 proteins were present at all time points and another 19 proteins were absent in the model group among those identified by MALD-TOF-MS. (3) Fuzheng Huayu Decoction down-regulated proteins and their expressions increased at 4 and 8 weeks, whereas it up-regulated those which decreased at 8, 12 and 16 weeks.
CONCLUSIONS(1) The changes in protein expressions, which effect metabolism, neuroendocrine function and cell proliferation, are the basis of liver fibrosis. (2) The anti-fibrotic effect of Fuzheng Huayu Decoction is holistic, specifically because it can decrease the abnormal cell proliferation and can increase the synthesis of normal proteins.
Animals ; Carbon Tetrachloride ; Carbon Tetrachloride Poisoning ; Drugs, Chinese Herbal ; therapeutic use ; Liver ; metabolism ; Liver Cirrhosis, Experimental ; drug therapy ; metabolism ; Male ; Phytotherapy ; Proteome ; metabolism ; Rats ; Rats, Wistar
9.Prophylactic effect of curcumin on hepatic fibrosis and its relationship with activated hepatic stellate cells.
Ya-jun HE ; Jian-chang SHU ; Xia LÜ ; Li FANG ; Yan SHENG
Chinese Journal of Hepatology 2006;14(5):337-340
OBJECTIVETo observe the prophylactic effect of curcumin on hepatic fibrosis and the number, location, apoptosis of activated hepatic stellate cells (HSCs) in the livers and to discuss the relationship between the prophylactic effects and activated HSC.
METHODSA rat model of hepatic fibrosis was established by intraperitoneal injection of carbon tetrachloride. Curcumin doses of 5 mg, 10 mg, 20 mg per 100 gram per 100g of body weight were given to three groups of the model rats. No curcumin was given to one group of the model rats and it served as the control. After eight weeks, all rats were sacrificed and their left liver lobes were examined histopathologically with H.E and Masson stainings. Grades of hepatic fibrosis were evaluated according to the SSS system. Activated HSC was detected by the alpha-SMA immunohistochemistry staining. HSC apoptosis was detected by double-stainings of terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) and desmin immunohistochemistry staining.
RESULTSDegrees (SSS system scores) of hepatic fibrosis in the curcumin groups were all less severe in comparison with those of the control group. Activated HSCs in the livers of the rats of the control group increased significantly compared with that of the treatment groups, and also fewer apoptotic HSCs were detected in the control group. On the contrary, fewer activated HSCs and more apoptotic HSCs were detected in the curcumin groups compared with those of the control group. The degrees of the effects were curcumin dose-dependent.
CONCLUSIONSCurcumin can prevent hepatic fibrosis. It can inhibit activation and proliferation of HSCs and induce HSCs apoptosis, which may be the mechanism(s) contributing to the prophylactic effects of curcumin on hepatic fibrosis.
Animals ; Apoptosis ; drug effects ; Carbon Tetrachloride ; Carbon Tetrachloride Poisoning ; Curcumin ; therapeutic use ; Enzyme Inhibitors ; therapeutic use ; Hepatocytes ; pathology ; Liver Cirrhosis, Experimental ; pathology ; prevention & control ; Rats ; Rats, Sprague-Dawley