Urantide减轻高脂饮食引起的大鼠非酒精性脂肪肝损伤

Urantide ameliorates the injury of high fat diet-induced non-alcoholic fatty liver in rats

目的探讨多肽化合物urantide对高脂饮食引起动脉粥样硬化大鼠非酒精性脂肪肝的保护作用。方法 72只SD大鼠随机分为:对照组(Con)、模型组(Mod)[用腹腔注射维生素D3(VD3)及高脂饮食方法复制大鼠动脉粥样硬化模型]、阳性药组(辛伐他汀,Sim)、urantide 3(Ut 3)、 7(Ut 7)及14 d组(Ut 14),给药剂量为30μg/kg。给药结束后,检测血清学及肝功能指标;HE染色胸主动脉、肝脏;RT-qPCR检测肝脏中尾加压素Ⅱ(UⅡ)、G蛋白偶联受体14(GPR14)的mRNA表达;免疫组织化学检测肝组织UⅡ、GPR14蛋白质表达。结果模型组大鼠血清中谷丙转氨酶氨酶(ALT)、谷草转氨酶(AST)等水平较对照组显著升高(P<0.05);urantide治疗组大鼠上述各项指标较模型组均显著回降(P<0.05);模型组大鼠肝脏中UⅡ及GPR14 mRNA与蛋白表达均较对照显著增高(P<0.05);与模型组大鼠相比,urantide治疗组随着给药时间的增加,UⅡ及GPR14 mRNA与蛋白表达显著回降(P<0.05)。结论 Urantide对高脂饮食所引起动脉粥样硬化大鼠非酒精性脂肪肝具有明显的保护作用。

Objective To investigate the effect of urantide on the nonalcoholic fatty liver in atherosclerosis rats. Methods Seventy-two SD rats were randomly divided into control,high-fat diet,positive drug group, urantide 3 d group,urantide 7 d group and urantide 14 d group.The model group was established by injecting a loading dose of vitamin D3 and feeding a high-fat diet.After 3,7 and 14 days of treatment the rats were sacrificed,measuring the TC, TG, LDL, AST, ALT and TBIL in blood serum,detect UⅡ and GPR14 mRNA and protein expression by Western blot and PCR respectively. Results With the increase of treatment dose and incubation time of urantide, fatty infiltration of the liver was significantly reduced, fat particles significantly decreased;liver function and blood lipids profile significantly improved;UⅡ and GPR14 mRNA and protein expression was significantly decreased. Conclusions Urantide can protect mice against non-alcoholic fatty liver disease.