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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 changes of C5aR and TGF-β_1 in renal tissue of rats with unilateral ureteral obstruction (UUO), so as to explore the role of C5αR in the occurrence of tubulointerstitial fibrosis The mechanism of action. Methods: Thirty-six male SPF SD rats were randomly divided into model group and sham operation group. Model group UUO surgery, sham-operated group only free ureter, not ligation. Six rats in each group were sacrificed on the 5th, 10th, 15th day after operation respectively. Hematoxylin and eosin (HE) and Masson staining were performed on the obstructed lateral renal tubules and detected by ELiVision TM (TM) plus plus immunohistochemistry Expression of C5αR and TGF-β_1 in tubulointerstitium. Results: In the model group, the renal tubule was dilated at day 5, the tubulointerstitial cells were partially degenerated, the tubulointerstitial cells were necrotic on the 10th day, and the interstitial fibrosis increased. On the 15th day, diffuse tubulointerstitial thickening and shrinkage, fibrosis Obviously (P <0.05). Immunohistochemistry results showed that only a small amount of TGF-β 1 and C5αR were expressed in the tubulointerstitial of sham-operated rats, and no significant changes were found with the passage of time. Expressions of C5αR and TGF-β 1 (P <0.05). The expression of C5αR increased significantly in the early stage of obstruction (day 5 to 10), but slightly increased in the late stage (day 11 to 15). CONCLUSION: The expressions of C5αR and TGF-β_1 in the obstructive side of model rats are up-regulated with prolonged obstruction, suggesting that C5αR may play an important role in the up-regulation of TGF-β1 in the early stages of renal interstitial fibrosis.