目的 通过构建蛋氨酸-胆碱缺乏（MCD）饮食诱导的小鼠非酒精性脂肪性肝炎（NASH）模型，研究小柴胡汤对NASH模型小鼠的保护作用。方法 选择C57BL/6小鼠为研究对象，将其随机分为对照组、模型组、小柴胡汤（高、中、低剂量）组、易善复组和强肝胶囊组。通过饲喂MCD饲料建立NASH模型，造模同时按分组给予不同药物进行干预；实验过程中记录小鼠体质量、日摄食量、日饮水量变化，实验结束对肝组织进行HE染色观察病理变化，检测血清生化指标丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、总胆固醇（TC）、三酰甘油（TG）、高密度脂蛋白胆固醇（HDL-C）、白细胞介素6（IL-6）和肿瘤坏死因子-α（TNF-α）的水平变化，检测肝组织中TC、TG的水平变化，利用qRT-PCR技术检测肝组织脂肪酸合成酶（FAS）和固醇调节元件结合蛋白1c（SREBP-1c）的表达水平。结果 小鼠体质量、日摄食量、日饮水量及肝脏系数等数据显示MCD饮食诱导的模型组小鼠会出现体质量降低、摄入量减少及肝脏湿质量下降的特点，而小柴胡汤给药组小鼠体质量、摄入量及肝脏系数较模型组小鼠显著升高；HE染色结果显示小柴胡汤可明显减轻肝组织脂肪变性和炎症程度，改善肝细胞的形态和结构；生化指标检测结果显示小柴胡汤能显著降低NASH模型小鼠血清及肝组织TG、TC水平，升高血清中HDL-C水平，降低血清中AST、ALT、IL-6、TNF-α水平；qRT-PCR结果显示模型组小鼠肝组织FAS和SREBP-1c的基因表达水平明显升高，小柴胡汤可显著降低FAS和SREBP-1c的基因表达水平。结论 小柴胡汤对MCD饮食诱导的NASH模型小鼠有明显保护作用，其机制可能通过调控抑制脂肪酸合成基因（FAS、SREBP-1c）的表达，减少脂肪堆积，实现调脂作用，并通过抑制炎症因子的表达改善肝组织的损伤。

Objective The protective effect of Xiaochaihu Decoction on non-alcoholic steatohepatitis (NASH) model mice was studied by constructing a methionine-choline deficiency (MCD) diet-induced NASH model in mice. Methods C57BL/6 mice, as the research objects, were randomly divided into normal control group, model group, Xiaochaihu Decoction (high, medium and low doses) group, Yishanfu group and Qianggan Capsule group. The NASH model was established by feeding MCD feeds, and model intervention was carried out at the same time by giving different drugs in groups; Changes in body weight, daily food intake, and daily water volume of the mice were recorded during the experiment. HE staining of liver tissue was performed at the end of the experiment to observe pathological changes. and the levels of biochemical indicator of alanine aminotransferase (ALT), Aspartate aminotransferase (AST), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) in serum, and the changes of TC and TG levels in liver tissue were detected, RT-PCR was used to detect the expression levels of fatty acid synthase (FAS) and sterol regulatory element binding protein 1c (SREBP-1c) in liver tissues. Results Data such as mouse weight, daily food intake, daily water intake, and organ coefficients indicated that MCD diet-induced model mice showed weight loss, decreased intake, and decreased liver wet weight. The weight, intake and liver coefficient of mice in Xiaochaihu Decoction group were significantly higher than those in the model group; The results of HE staining showed that Xiaochaihu Decoction could significantly reduce the degree of steatosis and inflammation of liver tissue, and improve the morphology and structure of liver cells; The results of serum biochemical indicators showed that Xiaochaihu Decoction significantly reduced the levels of TG, TC, AST, ALT, IL-6, TNF-α and increased the level of HDL-C in NASH model mice; RT-PCR results showed that the gene expression levels of FAS and SREBP-1c in the liver tissue of the model group mice were significantly increased, and the administration of Xiaochaihu Decoction could significantly reduce the gene expression levels of FAS and SREBP-1c. Conclusion Xiaochaihu Decoction has obvious protective effect on NASH mouse model induced by MCD diet. It may play a lipid-lowering role by regulating the expression of inhibitors of fatty acid synthetase genes (FAS, SREBP-1c), reducing fat accumulation, and inhibiting the expression of inflammatory factors to improve liver tissue damage.

R285.5

山东省重点研发计划（重大关键技术）项目（2017CXGC1301）；山东省重点研发计划（重大关键技术）项目（2016ZDJS07A21）；泰山学者工程专项经费项目（ts201511107）