目的 基于法尼醇X受体（FXR）通路探讨血脂康胶囊治疗小鼠代谢相关脂肪性肝病的作用机制。方法 C57BL/6J小鼠40只，按体质量随机分为对照组、模型组、多烯磷脂酰胆碱组、血脂康胶囊（0.3、0.6 g/kg）组，每组8只。对照组给予普通饲料，其余各组均给予高脂饲料复制小鼠代谢相关脂肪性肝病模型。多烯磷脂酰胆碱组ig 0.144 g/kg多烯磷脂酰胆碱胶囊、血脂康胶囊（0.3、0.6 g/kg）组分别ig 0.3、0.6 g/kg血脂康胶囊。对照组和模型组给予同体积生理盐水，连续给药4周。记录每组大鼠体质量、肝脏质量的变化，生化试剂盒测定各组小鼠血清三酰甘油（TG）、总胆固醇（TC）、高密度脂蛋白（HDL-C）、低密度脂蛋白（LDL-C）、天冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）和肝脏肿瘤坏死因子-α(TNF-α)和白细胞介素（IL）-6含量，油红O染色观察小鼠肝脏脂肪堆积情况，Western blotting测定各组小鼠肝脏FXR通路相关蛋白表达。结果 与模型组比较，血脂康胶囊组可显著降低小鼠肝脏质量、肝指数、TC、TG、ALT、AST、TNF-α、IL-6，升高HDL-C水平（P<0.05、0.01）；油红O染色显示，血脂康胶囊可明显降低脂滴在肝脏的堆积；Western blotting显示，与模型组比较，血脂康胶囊组可显著升高FXR蛋白表达，降低胆固醇7α羟化酶（CYP7A1）、肝受体同源物-1(LRH1)蛋白表达（P<0.05、0.01）。结论 血脂康胶囊治疗代谢相关脂肪性肝病的作用机制可能与干预FXR介导的脂代谢有关。

Objective To investigate the mechanism of Xuezhikang Capsules in treatment of metabolically associated fatty liver disease in mice based on the FXR pathway. Methods A total of 40 C57BL/6J mice were randomly divided into control group, model group, polyene phosphatidylcholine group, Xuezhikang Capsules（0.3 and 0.6 g/kg） group, with 8 mices in each group. Control group was fed with normal diet, and the other groups were fed with high-fat diet for 8 weeks to replicate the metabolically associated fatty liver disease model. Rats in polyene phosphatidylcholine were given 0.144 g/kg polyene phosphatidylcholine, Xuezhikang Capsules（0.3 and 0.6 g/kg） groups were given 0.3 and 0.6 g/kg Xuezhikang Capsules, respectively. Rats in control and model groups were given the same volume of normal saline for 4 weeks. Biochemical kits were used to determine the serum levels of TG, TC, HDL, LDL, AST, ALT, TNF-α, and IL-6. Oil red O staining was used to observe the liver fat accumulation. Western blotting was used to detect the expression of FXR pathway-related proteins in the liver of each group. Results Compared with the model group, the liver weight, liver index, TC, TG, ALT, AST, TNF-α, and IL-6 in the Xuezhikang Capsules group were significantly decreased, but HDL-C was increased（P＜0.05, 0.01）. Oil red O staining showed that Xuezhikang Capsules significantly reduced the accumulation of lipid droplets in the liver. Western blotting showed that compared with the model group, Xuezhikang Capsules group significantly increased the protein expression of FXR, and decreased the protein expression of CYP7A1 and LRH1（P＜0.05, 0.01）. Conclusion Xuezhikang Capsules can treat metabolically associated fatty liver disease possibly by interfering with FXR-mediated lipid metabolism.

R285.5

苏州工业园区东方华夏心血管健康研究院–天然调脂药物循证科研基金项目(2023-CCA-NLD-367)