目的 研究干擾素-α1b通過(guò)miR141抑制鋅指E盒結(jié)合同源蛋白1（ZEB1）/Smad相互作用蛋白1（SIP1）信號(hào)通路改善IgA腎病腎小管上皮細(xì)胞上皮–間充質(zhì)轉(zhuǎn)化（EMT）和纖維化的影響。方法 通過(guò)MDCK細(xì)胞模型驗(yàn)證干擾素-α1b對(duì)miR-141表達(dá)、ZEB1/SIP1信號(hào)通路的影響；構(gòu)建IgA腎病大鼠模型，按照隨機(jī)分為對(duì)照組、模型組、干擾素-α1b（15、30 μg）組、潑尼松組，每組8只，連續(xù)治療8周。監(jiān)測(cè)大鼠腎功能、炎癥因子水平、IgA沉積和腎臟病理變化；分析miR-141、ZEB1、SIP1、E-鈣黏蛋白（E-cadherin）的表達(dá)水平。結(jié)果 體外實(shí)驗(yàn)表明，干擾素-α1b能夠顯著上調(diào)MDCK細(xì)胞中miR-141的表達(dá)，并降低ZEB1和SIP1蛋白相對(duì)表達(dá)量（P＜0.05）。IgA腎病大鼠模型中，相比于模型組，干擾素-α1b組大鼠腎功能顯著改善，炎癥因子腫瘤壞死因子-α（TNF-α）和白細(xì)胞介素-6（IL-6）的分泌水平明顯降低，IgA沉積減少，腎臟損傷得到緩解（P＜0.05）。干擾素-α1b能誘導(dǎo)大鼠腎臟中miR-141顯著上調(diào)，抑制ZEB1和SIP1蛋白相對(duì)表達(dá)，上調(diào)E-cadherin蛋白相對(duì)表達(dá)，抑制上皮細(xì)胞EMT和纖維化（P＜0.05）。結(jié)論 干擾素-α1b通過(guò)上調(diào)腎臟中miR-141的表達(dá)，抑制轉(zhuǎn)錄因子ZEB1和SIP1表達(dá)，減少對(duì)E-cadherin的抑制，最終抑制腎小管上皮細(xì)胞EMT和纖維化，有效改善IgA腎病。

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

新疆少數(shù)民族科技人才特殊培養(yǎng)計(jì)劃科研項(xiàng)目（2023D03016）