荷叶碱对非酒精性脂肪肝模型小鼠肝组织中SREBP信号通路的影响

Effects of nuciferine on non alcoholic fatty liver disease and the relative mechanisms based on SREBP signaling pathway

关键词:  荷叶碱  非酒精性脂肪肝  SREBP信号通路

Key words:  nuciferine  NAFLD  SREBP signaling pathway

摘要:

[目的] 研究中药荷叶有效成分对非酒精性脂肪肝（NAFLD）模型小鼠的治疗作用及相关机制。[方法] 通过蛋氨酸和胱氨酸联合缺乏饲料建立NAFLD模型小鼠，同时灌胃不同剂量荷叶碱，通过考察造模给药后各组小鼠体质量及血清生化指标，同时对肝组织分别进行苏木精-伊红（HE）染色和油红O染色，研究荷叶碱对NAFLD模型小鼠的治疗作用。此外提取造模给药后各组小鼠肝组织总核糖核酸（RNA），荧光定量核酸扩增检测（qPCR）法检测各组小鼠肝组织中胆固醇调节元件结合蛋白（SREBP）通路相关基因表达，初步探究荷叶碱缓解NAFLD的作用机制。[结果] 荷叶碱能显著降低NAFLD模型小鼠体质量、血清丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）、总胆固醇（TC）及三酰甘油（TG）水平，同时荷叶碱可缓解NAFLD模型小鼠肝组织中脂肪变性，减少肝组织中脂质含量；此外，荷叶碱可下调NAFLD模型小鼠肝组织中SREBP通路相关基因SREBP-1、乙酰CoA羧化酶（ACC）、ATP-柠檬酸裂解酶（ACLY）及脂肪酸合酶（FASN）表达。[结论] 荷叶碱对NAFLD具有明显的疗效，其作用机制可能与抑制肝细胞SREBP通路激活相关。

Abstract:

[Objective] The aim of this study is to investigate the effects of active ingredient in lotus leaf on non alcoholic fatty liver disease (NAFLD) model mice and the relative mechanisms.[Methods] Mice was received high-fat diet to induce NAFLD. Meanwhile,mice were treated with different dosages of nuciferine orally. The effects of nuciferine on NAFLD were studied through measuring the body weight,serum biochemical markers after nuciferine treatment. The livers in each group were also stained with HE and oil red O to observe the pathological changes and lipid contents in liver. In addition,total RNAs in livers were isolated and the gene expression related to SREBP signaling pathway was measured using qPCR in order to study the underlying mechanisms of nuciferine on NAFLD.[Results] Nuciferine treatment significant decreased the body weight and serum levels of ALT,AST,TG and TC in NAFLD. Nuciferine could also attenuate the steatosis of hepatic cells and decrease the lipid content in liver. Compared with the NAFLD model mice,nuciferine treatment down-regulated the gene expression of SREBF-1,ACC,ACLY and FASN in liver.[Conclusion] Nuciferine could attenuate NAFLD in mice through inhibiting the activation of SREBP signaling pathway in liver.