Jiangzhuo Granule Improves Renal Fibrosis in a Model of Unilateral Ureteral Obstruction by Mediating the Hypoxia-inducible Factor-1α Pathway
Objective To investigate the mechanism of action of Jiangzhuo Granule in improving renal fibrosis via the hypoxia-inducible factor 1α(HIF-1α)pathway.Methods The unilateral ureteral obstruction (UUO)method was used to establish a model of renal fibrosis.The rats with renal fibrosis were randomly divided into model group,positive drug group,and Jiang-zhuo Granule group,with 6 rats in each group,and another 6 rats of the same size were selected as the sham-operation group.After 4 weeks of continuous intervention,HE staining and Masson staining were used to observe renal histomorphological changes,and the levels of creatinine (Cr),urinary protein (uPr),and microalbuminuria (MAU)were measured,as well as the levels of uric acid (UA),blood urea nitrogen (BUN),and Cr in blood;ELISA was used to measure the protein expression levels of interleukin-1β(IL-1β),interleukin-18 (IL-18 ),tumor necrosis factor-α(TNF-α),monocyte chemotactic protein-1 (MCP-1 ),α1-microglobulin (α1-MG),and retinol-binding protein-4 (RBP-4)in serum,and Western blot was used to measure the protein expression levels of HIF-1α and transforming growth factor-beta 1 (TGF-β1)in renal tissue.Results Jiangzhuo Granule sig-nificantly inhibited the proliferation of collagen fibers in the renal interstitium of UUO rats and significantly reduced the levels of urinary Cr,uPr,and MAU,the levels of Cr,BUN,UA,α1-MG,IL-1β,IL-18,MCP-1,and TNF-α in blood,and the levels of HIF-1α and TGF-β1 in renal tissue (P<0.05).Conclusion Jiangzhuo Granule can inhibit the progression of renal interstitial fibrosis and pro-tects renal function in UUO rats,possibly by inhibiting immune inflammatory response and regulating the HIF-1α pathway.
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