替米沙坦对非酒精性脂肪肝的保护作用

Protective Effect of Telmisartan on Nonalcoholic Fatty Liver Disease

目的观察替米沙坦对非酒精性脂肪肝的保护作用及其可能机制。方法 30只SD大鼠随机分为3组,正常对照组(NC,n=10),高脂组(HFC组,n=10)及替米沙坦干预组(HFT组,n=10),对照组给予正常饮食,高脂组及干预组给予高脂饮食,干预组在12周后开始给与替米沙坦[10mg/(kg·d)]灌胃4周。16周末采血检测肝功能、血脂,摘取肝脏组织行病理切片及real-time PCR、western blot的分子生物学检测。结果与NC组比较,HFC组的肝功能、血脂升高(P<0.05),肝脏脂肪病变明显,内质网应激相关蛋白GRP78、CHOP的mRNA表达水平升高(P<0.05),GRP78、ATF4和CHOP的蛋白表达升高;而HFT组较HFC组肝功能、血脂水平下降(P<0.05),肝脏脂肪病变改善,内质网应激相关蛋白的mRNA和蛋白表达水平均有下降。结论替米沙坦对NAFLD大鼠有保护作用,其机制可能是通过抑制内质网应激。

] Objective To investigate the protective effect of telmisartan on nonalcoholic fatty liver disease and its possible mechanism. Methods A total of 30 SD rats were randomly divided into 3 groups ： normal control group （ NC, n = 10 ）, high fat group（ group HFC, n = 10）and telmisartan intervention group （group HFT, n = 10 ）. The control group was given normal diet, the high-fat group and the intervention group were given high fat diet, and the intervention group was given telmisartan to the stomach （10mg/kg/d） for 4 weeks after 12 weeks. At the end of the 16 week, blood samples were collected to detect liver function and blood lipids ,while the liver tissues were harvested for pathological sections, real-time PCR, and Western blot molecular biological tests. Results Compared with group NC, the liver function and blood lipid of HFC group increased （ P 〈 0. 05 ） , the liver fatty lesion was obvious, the mRNA expression level of endoplasmic retieulum stress related protein GRP78 and CHOP increased（ P 〈 0. 05 ）, and the protein expression of GRP78, ATF4 and CHOP increased ; However, compared with group HFC, the liver function and blood lip- id level of group HFT decreased（ P 〈 0. 05 ） , the liver fat lesions improved, and the mRNA expression levels of endoplasmic reticu- lum stress related proteins and protein expression level in group HFI＂ both decreased. Conclusion Telmisartan has protective effect on NAFLD rats, and its mechanism may be by inhibiting endopiasmic reticulum stress.