Study On The Prevention And Therapeutic Effects Of Yinzhihuang Oral Liquid On Anti-Tuberculosis Drugs Induced Liver Injury

Objective To observe the effect of Yinzhihuang oral liquid on serum biochemical indexes and liver morphology of ATLI rats and explore the effect of Yinzhihuang oral liquid on the expression of CYP2E1,NAT2 and GSTM1 protein in ATLI rats,to study the methylation regulation mechanism of gene promoter region which may affect the expression of CYP2E1,NAT2 and GSTM1 proteins.Method According to the body weight number,48 SPF SD rats were randomly divided into 6 groups for preventive experiment(Yinzhihuang prevention group,ATLI model group,control group)and therapeutic experiment(Yinzhihuang treatment group,ATLI model group,control group).The levels of ALT,AST,TBIL and DBIL were detected by automatic blood biochemical analyzer,the protein expressions of CYP2E1,NAT2 and GSTM1 in rat liver tissue were detected by Western-blot,and the genomic DNA of rat whole blood was extracted by DNA extraction kit.Bisulfite sequencing and mass spectrometry were used to detect the methylation levels of CYP2E1,NAT2 and GSTM1.Results 1.Compared with the control group,the pathological changes in the ATLI model group were the most serious: obvious steatosis occurred,indicating that the liver injury of SD rats could be successfully induced by intragastric administration of Ethylamine pyrazine rifampicin(Ⅱ)at the dose of 1.89g/kg for21 days.2.In preventive experiments,Yinzhihuang oral liquid can reduce the levels of ALT,AST,TBIL and DBIL to some extent(P<0.05),reduce the degree of liver injury.In therapeutic experiments,Yinzhihuang oral liquid can reduce the levels of TBIL and DBIL to some extent(P<0.05),and reduce the degree of liver injury to a certain extent.3.Yinzhihuang oral liquid can reduce the protein expression of CYP2E1,NAT2 and GSTM1(P<0.05).4.There were n o differences in Cp G sites and overall methylation levels in the promoter region of CYP2E1,NAT2 and GSTM1 genes among different treatment groups in prevention and therapeutic experiments(P>0.05).Conclusions Yinzhihuang oral liquid can effectively reduce the levels of ALT,AST,TBIL and DBIL in ATLI rats and reduce the degree of liver injury.Yinzhihuang oral liquid has a certain preventive and therapeutic effect on ATLI rats.And Yinzhihuang oral liquid could down-regulate the protein expression levels of CYP2E1,NAT2 and GSTM1.No direct correlation was found between the methylation level of the promoter region of the three genes and Yinzhihuang oral liquid.