目的 基于法尼醇X受體（FXR）通路探討血脂康膠囊治療小鼠代謝相關(guān)脂肪性肝病的作用機制。方法 C57BL/6J小鼠40只，按體質(zhì)量隨機分為對照組、模型組、多烯磷脂酰膽堿組、血脂康膠囊（0.3、0.6 g/kg）組，每組8只。對照組給予普通飼料，其余各組均給予高脂飼料復(fù)制小鼠代謝相關(guān)脂肪性肝病模型。多烯磷脂酰膽堿組ig 0.144 g/kg多烯磷脂酰膽堿膠囊、血脂康膠囊（0.3、0.6 g/kg）組分別ig 0.3、0.6 g/kg血脂康膠囊。對照組和模型組給予同體積生理鹽水，連續(xù)給藥4周。記錄每組大鼠體質(zhì)量、肝臟質(zhì)量的變化，生化試劑盒測定各組小鼠血清三酰甘油（TG）、總膽固醇（TC）、高密度脂蛋白（HDL-C）、低密度脂蛋白（LDL-C）、天冬氨酸氨基轉(zhuǎn)移酶（AST）、丙氨酸氨基轉(zhuǎn)移酶（ALT）和肝臟腫瘤壞死因子-α(TNF-α)和白細胞介素（IL）-6含量，油紅O染色觀察小鼠肝臟脂肪堆積情況，Western blotting測定各組小鼠肝臟FXR通路相關(guān)蛋白表達。結(jié)果 與模型組比較，血脂康膠囊組可顯著降低小鼠肝臟質(zhì)量、肝指數(shù)、TC、TG、ALT、AST、TNF-α、IL-6，升高HDL-C水平（P<0.05、0.01）；油紅O染色顯示，血脂康膠囊可明顯降低脂滴在肝臟的堆積；Western blotting顯示，與模型組比較，血脂康膠囊組可顯著升高FXR蛋白表達，降低膽固醇7α羥化酶（CYP7A1）、肝受體同源物-1(LRH1)蛋白表達（P<0.05、0.01）。結(jié)論 血脂康膠囊治療代謝相關(guān)脂肪性肝病的作用機制可能與干預(yù)FXR介導(dǎo)的脂代謝有關(guān)。

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

蘇州工業(yè)園區(qū)東方華夏心血管健康研究院–天然調(diào)脂藥物循證科研基金項目(2023-CCA-NLD-367)