目的 本实验基于内质网应激-FXR途径探讨山柰酚（kaempferol， KAE）对高脂饮食诱导的小鼠肝脏脂质沉积的保护作用及其机制。 方法 高脂饲料喂养C57BL/6J雄性小鼠22周建立慢性非酒精性脂肪性肝炎（non-alcoholic steatohepatitis， NASH）模型，同时以不同浓度的KAE灌胃8周进行干预。评估肝脏脂质沉积变化，检测肝脏内质网应激相关蛋白表达，法尼醇X受体（farnesoid x receptor， FXR）信号活化情况和脂质合成相关基因的表达。在体外，以棕榈酸（palmitic acid， PA）刺激AML-12细胞诱导肝细胞脂质沉积。用siRNA干扰AML-12细胞FXR的表达，以评估KAE对内质网应激-FXR信号途径的作用。 结果 KAE显著抑制了高脂饮食引起的小鼠体质量快速增长，降低血清总胆固醇（TC）、总甘油三酯（TG）含量和谷丙转氨酶（ALT）活性（P < 0.05），有效改善肝脏大面积脂质沉积现象，对NASH小鼠肝脏脂质沉积具有保护作用。KAE降低肝脏GRP78、CHOP、p-PERK蛋白表达（P < 0.05），促进FXR及其活化标记蛋白质SHP的表达（P < 0.05），从而抑制脂肪酸合成酶（fatty acid synthase， FASN）的表达（P < 0.01），降低肝脏的脂合成。细胞实验显示，KAE能够降低PA暴露下AML-12细胞的内质网应激反应，提高FXR的表达和活性，抑制FASN的表达，进而抑制脂质合成。而FXR的敲除消除了KAE对SHP的促进作用和SHP介导的SREBP1c表达的抑制，进而消除了KAE对PA作用下AML-12细胞脂质沉积的保护作用。 结论 KAE通过缓解高脂环境下肝细胞的内质网应激，促进FXR/SHP信号通路，从而抑制脂质合成，改善肝脏脂质沉积，提示KAE具有成为防治NASH肝脏脂质沉积药物的潜力。

Objective To investigate the protective effects of Kaempferol （KAE） against hepatic lipid deposition induced by a high-fat diet， as well as the underlying mechanisms. Methods C57BL/6J male mice were fed a high-fat diet for 22 weeks to establish a chronic nonalcoholic steatohepatitis （NASH） model. KAE was administered during the last 8 weeks as an interventional agent to evaluate its effects. Liver lipid deposition was assessed， and the expression levels of endoplasmic reticulum （ER） stress-related proteins， activation of the Farnesoid X Receptor （FXR） signaling pathway， and the expression of lipid synthesis-related genes were analyzed. In vitro， palmitic acid （PA） was used to stimulate AML-12 cells to induce lipid accumulation. Additionally， siRNA targeting FXR was transfected into AML-12 cells to investigate the role of the ER stress-FXR signaling pathway in mediating the effects of KAE. Results The intervention of kaempferol inhibited the rapid weight gain induced by a high-fat diet， reduced serum total cholesterol， triglyceride levels， and ALT activity， effectively alleviated large-scale lipid aggregation in the liver， thereby exerting a protective effect against hepatic lipid deposition in NASH. Mechanistically， KAE decreased hepatic ER stress， promoted the expression of FXR and its activation marker SHP， thereby suppressing the expression of FASN and reducing hepatic lipid synthesis. In vitro， KAE treatment significantly reversed the inhibitory effect of excessive ER stress on FXR activity， as evidenced by the upregulation of FXR activity leading to decreased FASN expression and reduced steatosis in AML-12 cells. Moreover， FXR knockdown markedly abolished the protective effects of KAE on lipid deposition in AML-12 cells exposed to PA， by eliminating the promoting effect of KAE on SHP expression and the SHP-mediated suppression of SREBP1c. Conclusions KAE treatment alleviated ER stress， thereby enhancing FXR/SHP signaling and subsequently suppressing lipid synthesis to reduce hepatic lipid accumulation. These findings suggest that KAE holds therapeutic potential for the management of hepatic steatosis in NASH.