Purpose In order to explore whether TNF-α could regulate C3 expression in tubular epithelial cell which induced renal interstitial fibrosis after unilateral ureteral obstruction, while whether TNF-a receptor antagonist etanercept could reduce C3 expression in renal tubular epithelial cell which could alleviate renal interstitial fibrosis. Methods Wide type (WT) and C3 knock out (C3KO) mice were separately established to set up sham group and UUO group. Moreover, WT UUO mice were intraperitoneal injected with different concentrations of etanercept. Observed TNF-a and C3 expression in operated kidney after UUO in WT mice and C3KO mice, the correlation between TNF-a expression in operated kidney and C3 positive renal tubules, degree of operated kidney renal interstitial fibrosis. Observed TNFR, NF-κB p65, C3 expression in kidney tubular epithelial cell cytomembrane and degree of renal interstitial fibrosis after intraperitoneal injected with different concentrations of etanercept. Results Nearly all of kidney tubular epithelial cells cytomembrane were TNFR positive, some of kidney tubular epithelial cells cytomembrane were C3 positive, operated kidney was TNF-a strongly positive in WT and C3KO mice after UUO, and C3 positive renal tubules were strongly correlated with TNF-α positive cells which were infiltrated in renal insterium. Degree of renal interstitial fibrosis in C3KO UUO mice were alleviated when compared to WT UUO mice (P＜0.01). Expression of C3, NF-κB p65 in kidney tubular epithelial cells were reduced (P＜0.01)and degree of renal interstitial fibrosis were alleviated(P＜0.01)after etanercept treated in WT UUO mice. Conclusion After UUO, TNF-a and C3 were both participated in renal interstitial fibrosis. TNF-a regulated renal tubular epithelial cell C3 expression via renal tubule epithelial cell transcription factor NF-κB p65 which was involved in renal interstitial fibrosis, while the TNF-a receptor antagonism etanercept may block the pathway, and degree of renal interstitial fibrosis pathological changes were alleviated at last.%目的 探索TNF-α是否通过调控UUO小鼠肾小管上皮细胞补体3(complement 3,C3)水平介导肾间质纤维化(renal interstitial fibrosis, RIF)及相关机制,而TNF-α受体拮抗剂益赛普(etanercept)能否拮抗TNF-α作用减轻RIF.方法 将野生型(wide type, WT)与C3基因敲除(C3 knock out, C3KO)小鼠分别设置假手术(Sham)组、单侧输尿管结扎(unilateral ureteral ob. struction, UUO)组;另外,给WT UUO鼠腹腔注射不同浓度etanercept.观察WT UUO鼠及C3KO UUO鼠肾组织中TNF-α、C3的表达及TNF-α与表达C3肾小管的相关性及RIF程度;观察etanercept处理WT UUO鼠后各组肾小管上皮细胞表达TNF-α受体(TNF-α receptor, TNFR)、NF-KB p65、肾小管C3表达及RIF程度.结果 UUO鼠肾组织几乎所有肾小管上皮细胞均表达TNF-α受体(TNF-α receptor, TNFR)及UUO后肾组织高表达TNF-α,部分肾小管上皮细胞表达C3,表达C3肾小管周围有强阳性表达TNF-α细胞浸润;C3KO UUO组RIF程度较WT UUO组减轻(P＜0.01);经etanercept处理WT UUO鼠,肾小管C3和肾组织NF-KB p65表达均明显下降(P＜0.01),RIF减轻(P＜0.01).结论 UUO术后TNF-α、C3均参与RIF,TNF-α可能通过调控肾小管上皮细胞转录因子NF-κB p65的表达介导肾小管上皮细胞C3产生参与RIF,而etanercept可能拮抗TNF-α减轻RIF.
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