羟基红花黄色素A通过调节Sirt1抑制高脂诱导的非酒精性脂肪肝

Protective effect of hydroxysafflor yellow A against nonalcoholic fatty liver in high-fat diet induced mice by targeting Sirt1 signaling pathway

目的研究羟基红花黄色素A(HSYA)抗高脂饮食诱导小鼠非酒精性脂肪肝的作用及机制。方法将40只雄性小鼠随机分为Control组、模型组(HFD)、HSYA低剂量(HSYA-L,15 mg·kg^(-1))组和HSYA高剂量(HSYA-H,30 mg·kg^(-1))组。Control组喂养普通饲料,模型组、HSYA-L组和HSYA-H组喂养高脂饲料。药物组每日一次腹腔注射相应剂量的HSYA,12周后处死小鼠,HE染色进行肝组织病理学观察;全自动生化分析仪检测血清胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL);酶联免疫试剂盒测定谷丙转氨酶(ALT)及谷草转氨酶(AST);RT-PCR检测PPAR-γ、SCD1、FASN基因的表达水平,Western-blot检测肝脏组织中沉默信息调节因子1(Sirt1)蛋白表达。结果与正常组相比,模型组ALT、AST、TG、TC、LDL水平明显升高,HDL水平降低,HSYA给药组能够显著逆转这些指标的变化,减少肝脏脂肪含量(P <0.05)。模型组肝脏组织中PPAR-γ、SCD1、FASN基因表达升高,Sirt1蛋白表达下降,HSYA给药组能够提高肝组织中Sirt1蛋白表达,并降低PPAR-γ、SCD1和FASN基因的表达水平。结论 HSYA能够抑制高脂饮食诱导的小鼠非酒精性脂肪肝的发生,其机制可能是通过上调Sirt1信号通路发挥作用。

Objective To determine the protection of hydroxysafflor yellow A(HSYA) against nonalcoholic fatty liver disease in high-fat diet(HFD)-induced mice and the underlying mechanism.Methods Forty male mice were randomly divided into 4 groups: a control group, a model group, a low dose HSYA group(15 mg·kg^-1) and a high dose HSYA group(30 mg·kg^-1).Mice in the control group were given normal diet, and in the other groups were fed high-fat diet.HSYA-L and HSYA-H groups were administered HSYA at doses of 15 mg·kg^-1 and 30 mg·kg^-1,respectively.After 12 weeks, the mice were sacrificed and hepatic tissues were histopathologically observed by HE staining.Automatic biochemical analyzer was used to detect the level of TC, TG, HDL and LDL in the serum.AST and ALT were determined by ELISA kit.RT-PCR was used to detect the expression of PPAR-γ, SCD1 and FASN, and Western blot was used to detect the expression of Silent information regulation 1(Sirt1) protein in the liver tissue.Results Compared with the control group, the levels of ALT, AST, TG, TC and LDL were increased and the level of HDL was decreased in the model group.Administration of HSYA significantly decreased the levels of ALT, AST, TG, TC and LDL, increased the LDL level and reduced the lipid content in the liver tissue.At the same time, HSYA inhibited the expression of PPAR-γ, SCD1 and FASN mRNA levels and increased the expression of Sirt1 protein in the liver tissue.Conclusion HSYA may inhibit non-alcoholic fatty liver induced by HFD and the mechanism may involve the regulation of Sirt1 signaling pathway.