Studv on the role of renin angiotensin system in pathogenesis of nonalcoholic fatty liver disease / 中华消化杂志

ABSTRACT

Objective To investigate the role of renin angiotensin system (RAS) in pathogenesis of nonalcoholic fatty liver disease (NAFLD).Methods Twenty-four Wistar rats were evenly divided into control group and model group.The rats of control group were fed with normal diet,and model group were with high-fat diet.Rats were killed at the eighth week and serum liver function,blood lipid,glucose and insulin were tested.The liver tissues were stained with HE and Picro acid-Sirius red for pathological observation.The liver tissue concentration of angiotensin Ⅱ was determined by ELISA method and the expression of TGF-β1 in liver tissue was examined by immunohistochemistry.Results After eight weeks high fat feeding,weight,liver index,liver function,blood lipids and serum insulin of model group were significantly higher than those of control group (weight(463.50±22.72) g vs.(404.29±10.32) g; liver index(3.75±0.21) g vs.(2.66±0.15) g; ALT(79.8±8.6) U/L vs.(58.8±11.6) U/L; AST(200.01±51.72) U/L vs.(150.30±37.27) U/L; total cholesterol(3.67±0.48) mmol/L vs.(1.50±0.23) mmol/L; triglycerides(2.06±0.40) mmol/L vs.(0.71±0.34) mmol/L; insulin(17.37±2.89) pmol/L vs.(11.08±2.12) pmol/L),and all the differences were statistically significant (P＜0.01).The histopathological results of model group indicated liver steatosis,inflammatory reaction in part of lobule and portal area and significant fibrosis in part of liver tissue.The liver tissue angiotonin Ⅱ concentration of model group [(32.80 ± 2.81)pg/ml] was higher than that of control group [(22.83 ± 1.75) pg/ml,t =9.559,P＜0.01].The immunohistochemistry results showed that the expression of TGF-β1 of model group was obviously higher than that of control group (Z=-2.540,P =0.011 ).Spearman correlation analysis revealed that the increasing degree of angiotensin Ⅱ concentration was positively correlated with liver steatosis scores (r=0.644,P=0.002) and the expression of TGF-β1 (r=0.470,P=0.037).Conclusion The concentration of angiotensin Ⅱ and TGF-β1 increased in the livers of model rats,which indicated that RAS may participate in the pathogenesis and progress of NAFLD.