Abstract:

Objective To investigate the expression of monocyte-macrophage-related factors and interstitial fibrosis in kidney tissues of rats with ureter obstruction and recanalization. Methods Forty-eight male Spragur-Dawley rats were divided randomly into the obstructive group: sham (n=6), unilateral ureteral obstruction（UUO）3 days (n=6), UUO 7 days (n=6), and UUO 14 days (n=6) and recanalization group: bilateral ureteral obstruction（RBUO）0 day (n=6), 3 days after RBUO (n=6), 7 days after RBUO (n=6), and 14 days after RBUO (n=6). The kidneys were excised on day 3, 7, and 14, and the deposition of collagen fibers in kidney was detected with HE and Masson staining. Immunohistochemical analysis was performed to evaluate the protein expressions of monocyte chemoattractant protein-1 (MCP-1), macrophage colony-stimulating factor (M-CSF) and activated-macrophage marker CD68. Real-time PCR was used to detect the mRNA expressions of MCP-1 and M-CSF. TGF-β1 levels were determined by ELISA. Results Fibrosis observed with HE and Masson staining was obviously increased in kidney tissue of UUO rats, and aggravated as time prolonged, but alleviated in rats with recanalization. TGF-β1 levels were increased obviously in the UUO group, but decreased in rats with recanalization compared with those in BUO rats. In UUO rats, mRNA and protein expression levels of MCP-1 and M-CSF were increased. MCP-1 and M-CSF expression was gradually decreased in rats with recanalization compared with those in BUO rats. The dynamic change in expression of MCP-1 and M-CSF in both UUO rats and recanalization rats was consistent with the change in expression of CD68. Conclusion Dynamic change in expression of MCP-1 and M-CSF in kidney tissues reflects change of activated and accumulated monocyte-macrophages, which may be one of the major mechanisms contributing to fibrosis induced by ureter obstruction. Renal fibrosis is alleviated by down-regulated expression of monocyte-macrophages factors with recanalization operation.

Key words: Monocyte-macrophage, Chemoattractant factor, Ureter obstruction, Recanalization, Fibrosis, Immunohistochemistry, Real-time PCR, Rat