目的 研究干扰素-α1b通过miR141抑制锌指E盒结合同源蛋白1（ZEB1）/Smad相互作用蛋白1（SIP1）信号通路改善IgA肾病肾小管上皮细胞上皮–间充质转化（EMT）和纤维化的影响。方法 通过MDCK细胞模型验证干扰素-α1b对miR-141表达、ZEB1/SIP1信号通路的影响；构建IgA肾病大鼠模型，按照随机分为对照组、模型组、干扰素-α1b（15、30 μg）组、泼尼松组，每组8只，连续治疗8周。监测大鼠肾功能、炎症因子水平、IgA沉积和肾脏病理变化；分析miR-141、ZEB1、SIP1、E-钙黏蛋白（E-cadherin）的表达水平。结果 体外实验表明，干扰素-α1b能够显著上调MDCK细胞中miR-141的表达，并降低ZEB1和SIP1蛋白相对表达量（P＜0.05）。IgA肾病大鼠模型中，相比于模型组，干扰素-α1b组大鼠肾功能显著改善，炎症因子肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）的分泌水平明显降低，IgA沉积减少，肾脏损伤得到缓解（P＜0.05）。干扰素-α1b能诱导大鼠肾脏中miR-141显著上调，抑制ZEB1和SIP1蛋白相对表达，上调E-cadherin蛋白相对表达，抑制上皮细胞EMT和纤维化（P＜0.05）。结论 干扰素-α1b通过上调肾脏中miR-141的表达，抑制转录因子ZEB1和SIP1表达，减少对E-cadherin的抑制，最终抑制肾小管上皮细胞EMT和纤维化，有效改善IgA肾病。

Objective To investigate the effect of interferon-α1b on improving EMT and fibrosis of renal tubular epithelial cells in IgA nephropathy by inhibiting ZEB1/SIP1 signaling pathway through miR141. Methods MDCK cell model was used to verify the effects of interferon-α1b on miR-141 expression and ZEB1/SIP1 signaling pathway. Rats model of IgA nephropathy was established, and randomly divided into control group, model group, interferon-α1b (15, 30 μg) group, and prednisone group, with 8 rats in each group, for continuous treatment for 8 weeks. Renal function, levels of inflammatory factors, IgA deposition and renal pathological changes were monitored. The expression levels of miR-141, ZEB1, SIP1 and E-cadherin were analyzed. Results In vitro experiments showed that interferon-α1b could significantly up-regulate the expression of miR-141 in MDCK cells, and reduce the relative expression levels of ZEB1 and SIP1 proteins (P < 0.05). In the rat model of IgA nephropathy, compared the model group, the renal function of the rats in the interferon-α1b group was significantly improved, the secretion levels of inflammatory TNF-α and IL-6 were significantly decreased, the deposition of IgA was reduced, and the kidney injury was alleviated (P < 0.05). Interferon-α1b can induce significantly up-regulated miR-141 in rat kidney, inhibit the relative expression of ZEB1 and SIP1 proteins, up-regulate the relative expression of E-cadherin protein, and inhibit EMT and fibrosis in epithelial cells (P < 0.05). Conclusion Interferon-α1b effectively improves IgA nephropathy by upregulating the expression of miR-141 in the kidney, inhibiting the expression of transcription factors ZEB1 and SIP1, reducing the inhibition of E-cadherin, and ultimately inhibiting renal tubular epithelial cell EMT and fibrosis.

R965

新疆少数民族科技人才特殊培养计划科研项目（2023D03016）