补体C5α受体和转化生长因子-β_1在大鼠肾间质纤维化不同阶段肾组织的表达

Expression of Complement C5αReceptor and Transforming Growth Factor-β_1 in Different Stage of Rat Renal Interstitial Fibrosis

目的:动态观测补体C5α受体(C5αR)和转化生长因子-β_1(TGF-β_1)在单侧输尿管梗阻(UUO)大鼠肾组织的表达变化,从而探讨C5αR在肾小管间质纤维化发生中的作用机制。方法:将36只雄性SPF级SD大鼠随机分为模型组及假手术组。模型组行UUO术,假手术组仅游离输尿管,不结扎。术后第5、10、15天分别处死每组中的6只大鼠,取梗阻侧肾行苏木精-伊红(H-E)和Masson染色,并用免疫组织化学ELiVision^(TM)plus法检测肾小管间质中C5αR和TGF-β_1的表达。结果:模型组第5天肾小管扩张,小管间质细胞部分变性,第10天小管间质细胞可见坏死,间质纤维增多,第15天可见弥漫的肾小管基底膜增厚皱缩,纤维化明显(P<0.05)。免疫组织化学结果显示:假手术组大鼠肾小管间质中仅有少量TGF-β_1和C5αR表达,随时间延长未见明显变化;模型组大鼠梗阻侧肾组织中C5αR和TGF-β_1的表达随时间进展而明显增加(P<0.05),其中C5αR在梗阻早期(第5～10天)表达明显增多,而晚期(第11～15天)仅轻微增多。结论:模型组实验大鼠梗阻侧肾组织中C5αR和TGF-β_1表达随着梗阻时间延长而上调,提示C5αR可能在肾间质纤维化早期通过介导TGF-β_1的上调发挥作用。

Objective：To observe the expression of complement C5α receptor （C5αR） and transforming growth factor- β（TGF-β1）in renal tubular interstitium of unilateral ureteral obstruction （UUO） rats, and to investigate its role in renal interstitial fibrosis. Methods： 36 SPF male Sprague Dawley rats were divided into two groups： the model group and shamoperated group. The model group were performed UUO. The sham-operated group was dissociated left ureter only, and not to be obstructed. Six rats of each group were killed respectively at 5, 10, 15 d after surgery. Histological changes of renal tubular interstitium was observed by Hematoxylin--Eosine （HE） and Masson staining. Immunohistochemistry ELiVisionVMplus was performed on left renal tubular interstitium for TGF-β1 and C5αR in renal tubular interstitium at each time point. Results：The model group： on the 5th day renal tubular expansion, tubulointerstitial cell degeneration in part. On the 10th day tubulointerstitial cell can be seen necrosis, interstitial fiber increased. On the 15th day the tubular basement membrane thickened, collapsed, and obviously fibrosis （ P 〈 0. 05 ）. The results of immunohistochemistry showed that： C5αR and TGF-β1 were faintly stained in the sham-operated kidneys, and there was no significant change with the extension of the time. C5αR and TGF-β1 in obstructed renal tissues of the model group increased significantly with the extension of the time（P〈0. 05）. C5αR increased significantly starting from 5 to 10 d, but increased slowly from 11 to 15 d. Conclusions：The expression of CSαR and TGF-β1 in renaltissue of UUO rats was increased with the extension of the time, C5αR maybe take part in the earlier stage of renal fibrosis by upregulating TGF-β1.