目的 探讨人参皂苷Rh₄对顺铂致肠黏膜屏障功能损伤的作用机制。方法 ICR小鼠ig给予人参皂苷Rh₄（10、20 mg/kg）10 d，给药第7天单次ip顺铂（20 mg/kg）诱导肠损伤，对小鼠生化指标、肠组织病理变化进行观察，利用ELISA、免疫荧光染色和Western blotting探究血清中二胺氧化酶（diamine oxidase，DAO）活性、肠黏膜炎症反应、肠屏障功能和线粒体自噬相关蛋白的表达。利用顺铂致IEC-6细胞损伤筛选出最佳造模剂量，并采用不同浓度的人参皂苷Rh₄处理细胞，采用线粒体膜电位（mitochondrial membrane potential，MMP）试剂盒、流式细胞术和Western blotting探究人参皂苷Rh₄对顺铂致肠黏膜细胞凋亡、线粒体自噬相关蛋白表达的影响。结果 与对照组比较，顺铂组小鼠血清中DAO活性、炎症因子水平和肠组织丙二醛水平显著升高（P＜0.01、0.001），肠黏膜上皮紧密连接蛋白表达水平显著降低（P＜0.01），肠组织谷胱甘肽过氧化物酶（glutathione peroxidase，GSH-Px）和过氧化氢酶（catalase，CAT）活性显著降低（P＜0.01）；给予人参皂苷Rh₄干预后能显著逆转上述指标的变化（P＜0.05、0.01），并改善肠黏膜组织的病理学变化以及肠黏膜的通透性。与顺铂组比较，人参皂苷Rh₄能显著调控小鼠肠组织和IEC-6细胞中p21/p53/过氧化物酶体增殖物激活受体γ辅激活因子-1α（peroxisome proliferator-activated receptor γ coactivator-1α，PGC-1α）通路、线粒体自噬和凋亡相关蛋白表达（P＜0.05、0.01），显著升高顺铂致IEC-6细胞中MMP水平（P＜0.05、0.01）。结论 人参皂苷Rh₄通过调控线粒体自噬和凋亡途径改善顺铂致肠黏膜屏障功能损伤。

Objective To investigate the mechanism of ginsenoside Rh₄ on intestinal mucosal barrier damage induced by cisplatin.Methods ICR mice were orally administered with ginsenoside Rh₄ (10, 20 mg/kg) for 10 d. On the 7th day of administration, single ip cisplatin (20 mg/kg) was used to induce intestinal injury. Biochemical indicators and pathological changes in intestinal tissue were observed in mice. ELISA, immunofluorescence staining and Western blotting were used to explore the activity of diamine oxidase (DAO) in serum, intestinal mucosal inflammatory response, intestinal barrier function and expressions of mitochondrial autophagy related proteins. The optimal modeling dose was screened for cisplatin-induced IEC-6 cell damage, and cells were treated with different concentrations of ginsenoside Rh₄. The effects of ginsenoside Rh₄ on cisplatin-induced intestinal mucosal cell apoptosis and mitochondrial autophagy related protein expressions were investigated using mitochondrial membrane potential (MMP) assay kit, flow cytometry and Western blotting. Results Compared with control group, DAO activity in serum, levels of inflammatory cytokines in serum and malondialdehyde level in intestinal tissue of mice in cisplatin group were significantly increased (P < 0.01, 0.001), while the expression levels of tight junction protein in intestinal mucosal epithelium were significantly decreased (P < 0.01), activities of glutathione peroxidase (GSH-Px) and catalase (CAT) in intestinal tissue were significantly decreased (P < 0.01); After intervention with ginsenoside Rh₄, the changes in the above indicators were significantly reversed (P < 0.05, 0.01), and the pathological changes of intestinal mucosal tissue and intestinal mucosal permeability were improved. Compared with cisplatin group, ginsenoside Rh₄ significantly regulated the p21/p53/peroxisome proliferator activated receptor γ coactivator-1α (PGC-1α) pathway, mitochondrial autophagy, and apoptosis related protein expressions in intestinal tissue of mice and IEC-6 cells (P < 0.05, 0.01), and significantly increased MMP levels in cisplatin induced IEC-6 cells (P < 0.05, 0.01). Conclusion Ginsenoside Rh₄ improves cisplatin-induced intestinal mucosal barrier dysfunction by regulating mitochondrial autophagy and apoptosis pathways.

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吉林省科技发展计划项目（YDZJ202401674ZYTS）；吉林省卫生健康委员会青年扶持项目（2023JC031）；北华大学博士科研启动支持项目（20220027）；吉林省大学生创新创业训练计划项目（202310201257）