姜黄素调节SREBP和FAS改善非酒精性脂肪性肝病的研究

Curcumin alleviates non-alcoholic fatty liver disease by regulating SREBP and FAS

目的探究姜黄素对非酒精性脂肪性肝病(NAFLD)的作用和可能机制。方法18只SD大鼠随机分为对照组、模型组和姜黄素组,每组各6只。模型组和姜黄素组予以高脂高胆固醇食物10 ml/kg灌胃,对照组给予等量生理盐水灌胃。建模成功后,姜黄素组每日给予姜黄素100 mg/kg灌胃,对照组和模型组给予等量的羧甲基纤维素钠。治疗4周后,检测大鼠血清ALT、AST、甘油三酯(TG)和总胆固醇(TC)水平,HE染色观察大鼠肝脏组织病理学变化,免疫组织化学法检测大鼠肝组织固醇调节元件结合蛋白(SREBP)和脂肪酸合成酶(FAS)蛋白的表达情况,蛋白免疫印迹法检测沉默调节蛋白6(Sirt6)和磷酸化腺苷酸活化蛋白激酶(p-AMPK)蛋白表达变化。结果模型组ALT、AST、TG、TC、SREBP和FAS蛋白表达均高于对照组(P均<0.05);姜黄素组ALT、AST、TG、TC、SREBP和FAS蛋白表达均低于模型组(P均<0.05)。模型组Sirt6、p-AMPK蛋白表达均低于对照组(P均<0.05);姜黄素组Sirt6、p-AMPK蛋白表达均高于模型组(P均<0.05)。结论姜黄素可以减轻大鼠NALFD的脂肪沉积和肝损伤,可能与Sirt6、p-AMPK的表达上调相关。

Objective To explore the regulatory mechanism of curcumin in the treatment of nonalcoholic fatty liver disease(NAFLD).Methods Eighteen male SD rats were randomly divided into the control,model and curcumin treatment groups,6 rats in each group.In the model and curcumin treatment groups,NAFLD rat models were established by gavage with high-fat and high-cholesterol diet,and an equivalent amount of normal saline was given in the control group.After the model establishment,the rats were given with gavage with 100 mg/kg curcumin in the curcumin treatment group,and an equivalent amount of sodium carboxymethyl cellulose was given in the control and model groups.At 4 weeks after treatment,the serum levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST),triglyceride(TG)and total cholesterol(TC)were detected.Pathological changes of liver tissues were observed by HE staining.The expression levels of sterol regulatory element-binding protein(SREBP)and fatty acid synthase(FAS)proteins in liver tissues were characterized by immunohistochemical staining.The expression levels of silent information regulator 6(Sirt6)and phosphorylated adenylate-activated protein kinase(p-AMPK)proteins were measured by Western blot.Results In the model group,the expression levels of ALT,AST,TG,TC,SREBP and FAS proteins were significantly higher compared with those in the control group(all P<0.05).In the curcumin treatment group,the expression levels of ALT,AST,TG,TC,SREBP and FAS proteins were significantly lower compared with those in the model group(all P<0.05).In the model group,the expression levels of Sirt6 and p-AMPK proteins were significantly lower than those in the control group(both P<0.05).In the curcumin treatment group,the expression levels of Sirt6 and p-AMPK proteins were significantly higher than those in the model group(both P<0.05).Conclusion Curcumin can alleviate lipid deposition and hepatic injury in NALFD rats probably by up-regulating the expression levels of Sirt6 and p-AMPK.