丹酚酸B对ApoE敲除小鼠非酒精性脂肪肝的改善运用及其机制研究

Improvement and mechanism of salvianolic acid B on non-alcoholic fatty liver in ApoE knockout mice

目的探讨丹酚酸B通过调控AMPK诱导自噬对高脂诱导的ApoE敲除小鼠非酒精性脂肪肝病的影响。方法健康8周龄同源C57BL/6J小鼠和ApoE-/-小鼠鉴定后,随机分为对照组、模型组和SalB组,高脂饲料喂养,于第8周Sal B组腹腔注射SalB 15 mg·kg-1·d-1,对照组和模型组等剂量生理盐水。HE染色、油红O染色、Masson染色观察肝组织病理学特征,试剂盒检测血清中生化指标,免疫组化检测肝脏中炎症和氧化应激水平,Western blot法免疫荧光检测肝脏自噬和AMPK水平。结果模型组血清中AST、ALT明显升高,肝脏出现了大量的脂肪空泡和严重的脂质沉积并有胶原纤维增生,SalB干预后肝脏病变明显改善;模型组肝脏中炎症和氧化应激水平明显升高,SalB干预后明显降低;模型组肝脏中自噬和AMPK水平明显降低,SalB干预后明显增加。结论SalB可以改善ApoE-/-小鼠非酒精性脂肪肝病,其机制可能是通过调控ApoE-/-小鼠肝脏AMPK水平,提高自噬有关。

Aim To investigate the effect of salvianolic acid B(SalB)on non-alcoholic fatty liver disease in high fat-induced ApoE knockout mice by regulating AMPK-induced autophagy.Methods Healthy,8 weeks old,homologous C57BL/6J mice and ApoE-/-mice were randomly divided into control group,model group and Sal B group,fed with high fat diet,intraperitoneal injection of Sal B(15 mg·kg-1·d-1)in group Sal B on week 8,and control group and model group were given an equal dose of normal saline.Pathological changes of livers in each group were assessed by HE staining,oil red O staining and Masson staining.Biochemical indexes in serum were analyzed commercially available kits.The levels of inflammation and oxidative stress in liver were detected by immunohistochemistry.Autophagy and AMPK levels were determined by Western blot immunofluorescence.Results In model group,AST and ALT were significantly elevated in serum,and a large number of fat vacuoles and severe lipid deposits and collagen fibrosis were detected in liver.The liver lesions were significantly improved after SalB intervention compared with the ApoE-/-group.The levels of hepatic inflammation and oxidative stress significantly increased in model group but significantly decreased in SalB group.The levels of autophagy and AMPK were significantly reduced in model group and markedly elevated in SalB group.Conclusions Sal B can improve non-alcoholic fatty liver disease in ApoE-/-mice,and the mechanism may involve mediating AMPK level and enhancing autophagy levels in liver.