目的 基于体内与体外实验探讨姜黄素调控肠上皮细胞胆固醇代谢的潜在靶点及作用机制。方法 采用高脂喂养ApoE^-/-小鼠构建高胆固醇模型，给予姜黄素干预后，检测血清脂质水平；采用苏木素-伊红（hematoxylin-eosin，HE）染色观察小肠组织病理变化；Western blotting检测小肠组织低密度脂蛋白受体（low-density lipoprotein receptor，LDLR）、NPC1样细胞内胆固醇转运蛋白1（NPC1 like intracellular cholesterol transporter 1，NPC1L1）、三磷酸腺苷结合盒转运蛋白G8（adenosine triphosphate-binding cassette transporters G8，ABCG8）、ABCG5和肝脏X受体α（liver X receptor α，LXRα）蛋白表达。采用胆固醇胶束诱导大鼠小肠隐窝上皮细胞（intestinal epithelial cells-6，IEC-6）构建肠上皮细胞高胆固醇体外模型，给予姜黄素或LXRα抑制剂GSK2033干预后，采用油红O染色和免疫荧光检测脂质水平；Transwell实验检测胆固醇转运；Western blotting和免疫荧光检测胆固醇代谢相关蛋白表达。结果 体内实验表明，100、200 mg/kg姜黄素对高脂喂养的ApoE^-/-小鼠小肠组织结构无损伤，同时可降低小鼠体质量和血清脂质水平（P＜0.05），并调控胆固醇摄取与小肠经肠胆固醇排泄（transintestinal cholesterol excretion，TICE）途径相关蛋白的表达（P＜0.05、0.01）。体外实验蛋白谱的调控结果与体内模型一致，且姜黄素能够降低高胆固醇环境下肠上皮细胞脂质水平并抑制胆固醇转运（P＜0.05、0.01）。进一步使用LXRα抑制剂GSK2033干预后，细胞内脂质水平及TICE途径相关蛋白ABCG5、ABCG8和NPC1L1的表达均出现显著逆转（P＜0.05）。结论 肠上皮细胞LXRα是姜黄素促进胆固醇排泄、抑制胆固醇摄取，进而维持机体胆固醇稳态的一个重要靶点，且其作用可能还涉及其他调控通路。

Objective To investigate the potential targets and mechanism by which curcumin regulates cholesterol metabolism in intestinal epithelial cells based on both in vivo and in vitro experiments. Methods A high-cholesterol model was established in ApoE^-/- mice fed a high-fat diet, followed by intervention with curcumin, lipid levels in serum were measured. Hematoxylin-eosin (HE) staining was used to observe pathological changes in small intestine tissue. Western blotting was used to detect the protein expressions of low-density lipoprotein receptor (LDLR), NPC1 like intracellular cholesterol transporter 1 (NPC1L1), adenosine triphosphate binding cassette transporters G8 (ABCG8), ABCG5 and liver X receptor α (LXRα) in small intestine tissue. An in vitro high-cholesterol model was constructed in rat intestinal epithelial cells-6 (IEC-6) using cholesterol micelle stimulation. After intervention with curcumin or LXRα inhibitor GSK2033, lipid levels were detected by oil red O staining and immunofluorescence. Transwell experiment was used to detect cholesterol transport. Western blotting and immunofluorescence were used to detect cholesterol metabolism-related protein expressions. Results In vivo experiments showed that 100, 200 mg/kg curcumin caused no damage to small intestine tissue structure of ApoE^-/- mice fed with high-fat diet, and could reduce the body weight and lipid levels in serum of mice (P < 0.05), regulate the expressions of proteins related to cholesterol uptake and intestinal cholesterol excretion (TICE) pathway (P < 0.05, 0.01). The regulation results of protein profile in vitro experiments were consistent with the in vivo model, and curcumin could reduce the lipid levels of intestinal epithelial cells in a high cholesterol environment and inhibit cholesterol transport (P < 0.05, 0.01). After further intervention with LXRα inhibitor GSK2033, there was a significant reversal in intracellular lipid levels and expressions of TICE pathway related proteins such as ABCG5, ABCG8 and NPC1L1 (P < 0.05). Conclusion Intestinal epithelial LXRα is an important target of curcumin for promoting cholesterol efflux and inhibiting cholesterol uptake, thereby contributing to the maintenance of systemic cholesterol homeostasis, and its effects may also involve other regulatory pathways.

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湖南省自然科学基金项目（2024JJ5302）；血管生物学与转化医学湖南省重点实验室开放基金项目（2025XG002）；湖南中医药大学2025本科生科研创新基金项目（2025BKS120）；湖南中医药大学校级科研项目（自然科学类）（Z2023XJYB12）；湖南中医药大学2024年国家级大学生创新创业训练计划项目（S202410541107）；2025年度国家级大学生创新训练计划项目（202510541026）