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Effects And Mechanisms Of Paeoniflorin On Mice With Immunological Liver Injury

Posted on:2010-02-22Degree:MasterType:Thesis
Country:ChinaCandidate:X LiFull Text:PDF
GTID:2144360278450286Subject:Pharmacology
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Liver, which receive blood from portal vein, is the largest metabolic organ in the body. Faced with many insults such as ethanol, drugs, toxic agents, virus and bacteria, liver, which the number and state of activation of immunocyte resident in, is of much more difference compared with other immune organ. Severe inflammatory and injury can be initiated when faced with certain etiological factors, drug overdose, alcoholic intoxication, liver transplantation, fulminant hepatitis, extensive trauma, endotoxemia shock for instance,which leds to high mortality for disseminated intravascular coagulation and for multiple organ dysfunction syndrome during the acute inflammatory phase. The high mobidity of hepatitis is the main reason. Pathology showed hepatocyte degeneration, apoptosis and necrosis that are common causes of various liver diseases. Chronic liver injury can result in lose of its origin structure, gradually develop to cirrhosis and liver cancer. Therefore, positive and timely response to a variety of factors that cause liver damage will have important clinical significance.OBJECTIVE To investigate the effects and mechanisms of paeoniflorin (Pae) on mice with immunological liver injury (ILI) induced by Bacillus Calmette-Guérin (BCG) plus lipopolysaccharide (LPS)METHODS The model of ILI were induced by BCG plus LPS in mice. The activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) as well as the concentration of nitric oxide (NO) in serum were assayed by spectrophotometry. Malondiadehyde (MDA) content, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in liver homogenate were tested by the same method. ILI rats were induced by BCG plus LPS, too. Serum ALT and AST activities were assayed by the method mentioned above. The morphology changes in co-culture were observed on the 7th day. The effects of KC culture medium supplemented with different concentrations of Pae on HSC proliferation were detected by MTT assay. Hepatic tissue sections were stained with hematoxylin and eosin and examined under a light microscope.RESULTS (1) Pae (53,105,210 mg·kg-1) and TGP (85 mg·kg-1) ig were able to reduce mortality of ILI mice induced by BCG plus LPS. (2) Liver index, spleen index, and serum transaminase activities (ALT, AST) in ILI mice treated with various dose of Pae were significantly decreased compared with their counterpart in the model group. The area and extent of necrosis as well as the infiltration of inflammatory cells in hepatic tissue sections of ILI mice were attenuated. (3) KC supernatants could promote the HSC proliferation. KC supernatants treated with Pae could decrease the promoting effects of KC on HSC proliferation.CONCLUSION Paeoniflorin can ameliorate ILI in mice and decrease effects of KC on promoting HSC proliferation. The underlying mechanism may correlated with its ability of free radical scavenging, increasing the activities of SOD and GSH-Px.
Keywords/Search Tags:paeoniflorin, total glucosides of paeony, immunological liver injury, kupffer cells
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