Study On The Effect And Mechanism Of Captopril On Rat Model Of Non-alcoholic Fatty Liver

Objective:To observe the effect of capsule of captopril on rat model of nonalcoholic fatty liver and tentatively explore the mechanism. Methods: Eighty male SD rats were randomly divided into two groups:normal control group and high fat diet group. One week later, normal control group fed with regular chow, the other groups fed with high fat diet(regular chow+10% lard+2% cholesterol+0.2% sodium cholate). During the experimental period, all the rats were free to drink and eat. Six weeks later, high fat diet group was randomly divided into five groups: model control group, rosiglitazone control group, and treatment group of low, medium and high dose. Rosiglitazone control group and the three treatment groups were given the same capacity rosiglitazone and low, medium, high dose captopril, respectively; normal control group and model control group were given the same capacity distilled water, once a day. Another six weeks later, after absolute diet 12h, all the rats were weighed and were anesthetized with 2% pentobarbital sodium. Then they were sacrificed. The serum levels of fasting blood glucose (FBG), total cholesterol(TC), triglyceride(TG), alanine aminotransferase (ALT), aspartate aminotransferase(AST) were determined by using automatic biochemical analyzer; the contents of malondialdehyde (MDA), glutathione (GSH), fasting insulin (INS), leptin(LEP) were measured by thibabituric acid method (TBA), colorimetry, radioimmunoassay (RIA), enzyme-linked immunosorbent assay (ELISA), respectively. The livers were weighed. Then the same part of livers was selected and made hematoxylin-eosin staining. The pathological changes in those hepatic tissues were observed under light microscope. The levels of TG、TC in liver tissue were determined by enzyme coupling colorimetric method and the mRNA expression of CYP2E1 in liver tissue were detected by reverse transcription-polymerase chain reaction (RT-PCR). According to the formulas, the insulin resistance index(IRI)、insulin sensitive index (ISI) and liver index were counted. Results:Compared to normal control group, the levels of FBG, INS, TC, TG, LEP, ALT, AST, MDA, liver index and IRI rose significantly(P<0.01 or P<0.05), the mRNA expression of CYP2E1 increased(P<0.01) in model control group. Also, the levels of ISI and GSH decreased (P<0.01). Compared with model control group, the levels of FBG, INS, TC, TG, LEP, ALT, AST, MDA, IRI, liver index and the mRNA expression of CYP2E1 decreased signiflcantly(P<0.01 or P<0.05) in high dose captopril treatment group, the levels of ISI and GSH decreased(P<0.01 or P<0.05); the levels of FBG, INS, TC, TG, LEP, MDA, IRI, liver index and the mRNA expression of CYP2E1 decreased significantly(P<0.01 or P＜0.05) in rosiglitazone control group, the levels of ISI decreased(P<0.01 or P<0.05).About the pathological observations by light microscope, model control group showed:there was extensive hepatic steatosis, mainly for the macrovesicular steatosis; the liver cells were arranged disorderly and appeared edema; a large number of cells inflammatory infiltrated. High dose captopril treatment group showed:there was a little hepatic steatosis, mainly for the microvesicular steatosis; most liver cells were arranged in right order, and some liver cells appeared edema; a small number of cells inflammatory infiltrated. The pathological changes of rosiglitazone control group were similar to high dose captopril treatment group, except that rosiglitazone control group existed more macrovesicular steatosis. Conclusion:The rat models of nonalcoholic fatty liver were successfully established. Captopril can decrease hepatic steatosis, and have certain preventive and therapeutic effects on nonalcoholic fatty liver disease. Captopril can improve nonalcoholic fatty liver disease by reducing insulin resistance and augmenting antioxidant capacity.