Studies On GSTA1, The Early Indicator Of Acute Hepatic Injury And Screening Liver Protecting Medicines Preliminarily

With the development of economy, environmental pollution, food and drug safety events havehappened frequently. It leads liver diseases showed a rising trend year by year. Hepatic injury is one ofthe key diseases, which endager human health. Acute hepatic injury that causes the development ofdisease and developing into liver failure finally is the initiating factor and common pathway of numerousliver diseases. The target is to find the indicator of acute heptic injury with earlier period and moresensitive. GSTA1is a subtype of GST. It is also be an important part of the body′s antioxidant defensesystem in encoded dimer protein. Catalyzed many xenobiotics with GSH, promote degradation and clear,protect the body. Clear and definite the change of GSTA1is a new stage in acute hepatic injury. Theresearch is based on the animal modeland the indicator of acute hepatic injury, screening the effectivemedicine of protects the hepatic injury. Lay the foundation in screening the hepatoprotective medicinefor APAP-induced model and the alcohol-induced model.The research used male KM mice as experimental animals. And the research based on the threemice models of acute liver injury. Such as the CCl₄-induced model, the APAP-induced model and thealcohol-induced model. Based on the three models which were established by laboratory, selected thepoint of time-respones and does-respones. Compared with GSTA1and the by means, and then analysisand evaluation. The concentration of GSTA1was detected by mouse GSTA1kit with the principle isElisa; the activity of ALT was detected by ALT kit with the principle is colormetry. On this basis,screening the effective medicine of the CCl₄-induced model by levels of serum transaminase（ALT,AST）, liver homogenates indicators （SOD, MDA, GSH, GSH Px）, concentration and activity of GSTA1.After determining the effective medicine and the optimal dosage was determined by levels of serumtransaminase（ALT, AST）, liver homogenates indicators （SOD, MDA, GSH, GSH-Px） concentrationand activity of GSTA1and liver histology analysis.The result shows:1. Chemical hepatic injury in time-respones, by statistic analysis, gavage0.35%carbontetrachloride for6h, the changes of GSTA1had significant difference compare with controlgroup（P<0.01）;16h, the changes of ALT had difference compare with control group（P<0.05）;24h, thechanges of GSTA1and ALT reached maximum. In dose-respones, by gavage0.125%carbontetrachloride, the changes of GSTA1had significant difference compare with control group（P<0.01）; bygavage0.3%, the changes of ALT had significant difference compare with control group（P<0.01）.2. Drug-induced acute hepatic injury in time-respones, by statistic analysis, gavage200 mg·kg^-1body weight APAP for2h, the changes of GSTA1had significant difference compare withcontrol group（P<0.01）; gavage for8h, the changes of ALT had significant difference compare withcontrol group（P<0.05）;12h, the changes of GSTA1and ALT reached maximum. In dose-respones, bygavage100mg·kg^-1body weight APAP, the changes of GSTA1had significant difference compare withcontrol group（P<0.01）; by gavage200mg·kg^-1body weight APAP, the changes of ALT had significantdifference compare with control group（P<0.01）.3. Alcoholic hepatic injury in time-respones, by statistic analysis, by gavage50%ethanol,14mL·kg^-1, for2h, the changes of GSTA1had significant difference compare with control group（P<0.01）;6h, the changes of ALT had difference compare with control group（P<0.05）;8h, the changes of GSTA1and ALT reached maximum; ALT had a crest value in12h. In dose-respones, by gavage50%ethanol,10mL·kg^-1, the changes of GSTA1had significant difference compare with control group（P<0.01）;12mL·kg^-1, the changes of ALT had difference compare with control group（P<0.05）;14mL·kg^-1, thechanges of ALT had significant difference compare with control group（P<0.01）.4. In medicine effective test, by detecting serum transaminase （ALT, AST）, liver homogenatesindicators （SOD, MDA, GSH, GSH-Px）, and GSTA1. Compared with the control group: model grouphad significant difference（P<0.01）, so it was established successfully; both total glucosides of paeonyand grape seed had significant difference（P<0.01）; Silymarin and Solanum nigrum had no difference. Inthe test, determine the Solanum nigrum was the best one.5. In determining optamal dose test, by detecting serum transaminase （ALT, AST）, liverhomogenates indicators （SOD, MDA, GSH, GSH-Px）, GSTA1and liver histology analysis. Comparedwith the control group the high does of Solanum nigrum had no difference.So the optimal dose ofSolanum nigrum is150mg·kg^-1.The research shows in acute hepatic injury, the serum GSTA1would detective both in early and lowconcentration in acute hepatic injury. As the indicator of hepatic injury GSTA1is more accurate andsensitive. Therefore, GSTA1could be an early indicator of acute hepatic injury in mice. At the same time,the research screened the effective medicine for chemical acute hepatic injury and determined theoptimal dose. It would be a foundation for other models to screen the effective medicine.