The Therapeutic Effect Of Captopril On Early Stage Alcoholic Fatty Liver Rat And The Study Of Its Mechanism

Objective:To build a model of alcoholic fatty liver disease in rats,explore the curative effect of captopril on it and discuss the possible mechanism pertaining to it.Method:127 rats,randomly divided into two groups:13 in the normal group,114 in the mould group,and10 days after adaptive feeding.The module gives alcohol to the stomach,with alcohol 0.8ml·100g^-11 at 35%for the first week,and isomeric saline twice a day?9 a.m.and 3 p.m.?in the normal group.The module group was then given an increase of 5%per week in dietary alcohol at a dose of 0.8 ml·100g^-1,twice a day,unchanged in the normal group.When concentrations increased to50%in the fourth week,rats were found to have started to die in large numbers and recovered to 45%in the fifth week,after which they remained at 0.8ml·100g^-1,twice a day.After 6 weeks,4 rats were randomly selected for liver pathology examination,and it was confirmed that there was alcoholic hepatitis and a small amount of fatty liver.The remaining 92 rats in the module group were randomly divided into 5 groups,19 in the model group,19 in the high dose group of captopril,18 in the medium dose group of captopril,18 in the low dose group of captopril,18in the water thistle positive control group,with 45%continued to be fed with alcohol,at a dose of 0.8ml·100g^-11 twice a day,with gastric administration commencing at an equivalent dose for both adult and rat body surface,For six weeks.Captopril was given2.7 mg·100g^-1?twice the adult equivalent?in the high dose group,captopril 1.35 mg·100g^-1?equivalent to the adult equivalent?in the medium dose group,captopril 0.675 mg·100g^-1?equivalent to the adult equivalent?in the low dose group,Water thistle positive control group was given water thistle 3.78mg·100g-1?equivalent to adult equivalent dose?.Give the drug once a day between two alcohol intakes?12 noon?;Equilibrium 0.9%sodium chloride injection was given in normal and model rats.All rats fed and drank freely throughout the experiment.By the end of the 12th week,all the rats had 12 hours of fasting then they were weighed with electronic scale,and anesthetized with 1%pentobarbital sodium(0.4ml·100g^-1),followed by killing and anatomy,their blood was drawn from the abdominal aorta by 3-5ml and put into a biochemical blood collection tube for centrifugation and supernate.Fully automatic biochemical analyzer was used to detect the rat's Alanine aminotransferase?ALT??Aspartate aminotransferase?AST??high density lipoprotein cholesterol?HDL-C?and low density lipoprotein cholesterin?LDL-C?;The rat's liver was separated and weighed for liver wet weight,the liver index was calculated,then the hepatic tissue was taken from the same position for hematoxylin-eosin staining?HE?,then it was placed under a light microscope to observe its pathological change;another hepatic tissue was taken from the same position for a tissue homogenate with ice-water bath.Fully automatic biochemical analyzer was used to detect the rat's level of Total cholesterol?TC?and Triglyceride?TG?;enzyme linked immunosorbent assay?ELISA?was used to measure the level of nuclear transcription factor?NF-?b?and tumor necrosis factor?TNF-??,Uv visible spectrophotometry.method?UV-Vis?was used to measure the level of malondialdehyde_MDAand glutataione_GSH-Px,Western Blot was used to detect the level of expression of protein of CYP2E1 in the hepatic tissue of rats.Result:the model control group was found to have an increase in liver wet weight,liver index,TC?TG?ALT?AST?GGT?LDL-C?MDA content,NF-?b?TNF-??and the expression of protein of CYP2E1 in the hepatic tissue,and a decline in level of HDL-C and GSH-Px,the difference between it and the normal control group was significant?P<0.05?,The captopril high-dose group was found to have a decline in liver wet weight,liver index,TC?TG?ALT?AST?GGT?LDL-C?MDA content,NF-?b?TNF-??and the expression of protein of CYP2E1 in the hepatic tissue and an increase in level of HDL-C and GSH-Px,the difference between it and the model control group was significant?P<0.05?The positive control group was found to have a decline in liver wet weight,liver index,TC?TG?ALT?AST?GGT?LDL-C?MDA content,NF-?b?TNF-??and the expression of protein of CYP2E1 in the hepatic tissue and an increase in level of HDL-C and GSH-Px,the difference between it and the model control group was significant?P<0.05?Pathological Examination of liver tissue section under optical microscope showed that,large amount of diffuse fatty degeneration was found in the model control group,mostly macro-vesicular fatty degeneration,hepatocyte edema was also visible and the cell arrangement was disordered,and a large number of inflammatory cell infiltration was also visible.A small amount of fatty degenerations were found in the captopril high-dose group,mostly micro-vesicular fatty degeneration,it was found that,most of the liver cell arrangement was normal,with less cell edema,and less inflammatory cell infiltrations.The captopril medium and low-dose group were found to have partial fatty degenerations,macro-vesicular fatty degeneration and micro-vesicular fatty degeneration,in some regions the hepatocytes were normally arranged,cell edema and inflammatory cell infiltration was still visible in some regions.The pathological observation of silymarin-positive control group was similar to that of captopril high-dose group,only different in that,the fatty degeneration was slightly reduced,and still some of them were macro-vesicular fatty degenerations.Conclusion:The experimental modeling of alcoholic fatty liver in SD male rats is successful,and the experiment shows that captopril could reduce the fatty degeneration of hepatocyte of SD male rats,enhance the antioxidant stress ability of SD male rats,and have some preventive and therapeutic effects on alcoholic fatty liver.