The effects of renin-angiotensin system blockade on the liver steatosis in rats on long-term high-fat diet / 中华内科杂志

ABSTRACT

Objective To observe the relationship between liver steatosis in rats with long-term high-caloric and high-fat diet and the expression of angiotensinogen(AGT)、uncoupling protein 2(UCP-2)and transforming growth factorβ1(TGFβ1).Then angiotensin-converting enzyme inhibitor(ACEI)and angiotensin Ⅱ receptor blocker(ARB)drugs were given to investigate whether rennin-angiotensin system (RAS)blockade can mitigate the liver steatosis and to probe its mechanisms.Methotis Forty male Wistar rats were divided into normal control group(NC group,n=10),high-calorie and high-fat fed group(HF group,n=10),ARB treated group(AR group,n=10)and ACEI treated group(AE group,n=10).Rats were fed with high-calorie and high-fat diet and given RAS inhibitor drugs(valsartan 40mg/kg to the AR group and perindopril 4 mg/kg to the AE group)for eight weeks.Serum TG,free fatty acids(FFAs) lever and the fat content in liver were then measured with biochemical tests;insulin resistance was evaluated with euglycemic hyperinsulinemia clamp technique,the expression of UCP-2 and TGFβI in liver tissue were examind with immunohistochemical staining and AGT mRNA,UCP-2 mRNA and TGFβ1 mRNA were tested with RT-PCR.Results With the administration of RAS inhibitor drugs,following changes were observed.The levels of TG and FFAs and the fat content in liver decreased(P＜0.01 or P＜0.05),insulin resistance in high-fat fed rats was improved(P＜0.05),liver steatosis,inflammation and fibrosis were mitigated.The levels of UCP-2 decreased by 36.5%(P＜0.05)in AE group and 42.5%(P＜0.05)in AR group and TGFβ1 decreased by 37%(P＜0.05)in AE group and 41.6%(P＜0.05)in AR group as compared with the HF group with immunohistochemical staining.The expression of AGTmRNA decreased by 14.9%(P＜0.05)in AE group and 21%(P＜0.05)in AR group,UCP-2 mRNA decreased by 9%(P＜0.05)in AE group and 11%(P＜0.05)in AR group and TGFβ1 mRNA decreased by 17%(P＜0.05)in AE group and 19%(P＜0.05)in AR group as compared with the HF group with RT-PCR.Conclusions RAS blockade could improve insulin resistance,mitigate the liver injury of long term high-fat fed rats and have a protective effect on liver.The mechanism may be associated with the effects of improved insulin resistance,the interaction within RAS and the down-regulation of UCP-2 and TGFβ1 in liver tissue.