基于烟酰胺磷酸核糖转移酶(NAMPT)探讨红景天苷在非酒精性脂肪性肝病小鼠模型中的保护作用

Role of salidroside in a mouse model of non-alcoholic fatty liver disease:A study based on nicotinamide phosphoribosyltransferase

目的研究红景天苷对非酒精性脂肪性肝病(NAFLD)的保护作用,并探讨其作用机制。方法将24只雄性KM小鼠随机分为正常组、高脂饮食(HFD)组、HFD+空白对照组、HFD+红景天苷组,每组6只,正常组小鼠予以普通饲料喂养,其余各组高脂饮食,造模14周开始给予100 mg·kg^(-1)·d^(-1)红景天苷灌胃给药,22周末取材。酶联免疫法测定血清ALT、AST、TG、TC、HDL-C、LDL-C等相关生化指标;HE染色和NAFLD活动评分(NAS)观察小鼠肝组织病理。Western Blot检测肝组织内烟酰胺磷酸核糖转移酶(NAMPT)、Sirt1、AMPKα、SREBP1的表达变化。多组间比较采用单因素方差分析,进一步两两比较采用LSD-t检验。结果与正常组比较,HFD组小鼠肝组织存在广泛较大的脂肪滴,脂肪变性明显,NAS评分升高(P<0.01),外周血AST、ALT、TG、TC、LDL-C的含量明显增高(P值均<0.05),HDL-C含量降低(P<0.05),肝组织内NAMPT、AMPKα、Sirt1的表达降低(P值均<0.05),SERBP1的表达增加(P<0.01)。而HFD+红景天苷组较HFD组、HFD+空白对照组肝组织空泡状脂滴分布、小叶内炎症减少,肝细胞气球样变减轻,NAS评分下降(P<0.01),外周血AST、ALT、TG、LDL-C的含量明显降低(P值均<0.05),HDL-C含量升高(P<0.05),NAMPT、AMPKα、Sirt1的表达增加(P值均<0.05),SERBP1的表达减少(P<0.01)。结论红景天苷能明显改善高脂饮食诱导小鼠NAFLD的病理状态,并通过增加NAMPT、Sirt1、AMPKα的表达,减少SERBP1的表达,发挥其对NAFLD的保护作用。

Objective To investigate the protective effect of salidroside against nonalcoholic fatty liver disease(NAFLD)and its mechanism of action.Methods A total of 24 male KM mice were randomly divided into normal group,HFD group,HFD+blank control group,and HFD+salidroside group,with 6 mice in each group.The mice in the normal group were given normal diet,and those in the other groups were given high-fat diet.After 14 weeks of modeling,the mice were given salidroside 100 mg/kg/day by gavage,and related samples were collected at the end of week 22.Enzyme-linked immunosorbent assay was used to measure the serum levels of related biochemical parameters including alanine aminotransferase(ALT),aspartate aminotransferase(AST),triglyceride(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C);HE staining and NAFLD activity score(NAS)were used to observe the liver histopathology of mice;Western blot was used to measure the changes in the expression of NAMPT,Sirt1,AMPKα,and SREBP1 in liver tissue.A one-way analysis of variance was used for comparison between multiple groups,and the least significant difference t-test was used for further comparison between two groups.Results Compared with the normal group,the HFD group had obvious steatosis and extensive large lipid droplets in liver tissue,with significant increases in NAS score(P<0.01)and the content of AST,ALT,TG,TC,and LDL-C in peripheral blood(all P<0.05)and a significant reduction in the content of HDL-C(P<0.05),as well as significant reductions in the expression levels of NAMPT,AMPKα,and Sirt1 in liver tissue(all P<0.05)and a significant increase in the expression level of SERBP1(P<0.01).Compared with the HFD group and the HFD+blank control group,the HFD+salidroside group had reductions in the distribution of vacuolar lipid droplets and intralobular inflammation in liver tissue,alleviation of the ballooning degeneration of hepatocytes,significant reductions in NAS score(P<0.01)and the content of AST,ALT,TG,and LDL-C in peripheral blood(all P<0.05),and a significant increase in the content of HDL-C(P<0.05),as well as significant increases in the expression levels of NAMPT,AMPKα,and Sirt1 in liver tissue(all P<0.05)and a significant reduction in the expression level of SERBP1(P<0.01).Conclusion Salidroside can significantly improve the pathological state of mice with NAFLD induced by high-fat diet and exert a protective effect against NAFLD by increasing the expression of NAMPT,Sirt1,and AMPKαand reducing the expression of SERBP1.