Objective To investigate the therapeutic effect and mechanism of pirfenidone(PFD)on kidney of rats with renal fibrosis.Methods Thirty SD rats were randomly divided into control group model group,and treatment group with equal number.The latter two groups were intraperitoneally injected with 50％CCl4 oil solution to establish a renal fibrosis model.The control group was intraperitoneally injected with the same dose of olive oil for 5 weeks.At the end of modeling,the treatment group rats were given PFD aqueous solution by gavage,while the model group and contro group were given the same dose of normal saline by gavage for 4 weeks.During the experiment,the activity,food and water intake,hair color,and bowel movements of rats were observed daily.The rats were weighed,their body mass and general condition were recorded before the experiment,and on the 2nd,5th,7th after intervention,and 24 h after the last dose of the 9th week.At the end of the 9th week of experiment,all groups of rats were euthanized.Heart blood was collected and tested for blood urea nitrogen(BUN),serum creatinine(Scr),and uric acid(UA)levels.Renal tissue was stained with Hematoxylin-Eosin(HE)and Masson's staining to observe the degree of renal tissue damage and fibrosis.Western Blot assay was adopted to test the expression of silence information regulator 3(SIRT3),hypoxia-inducible factor-1α(HIF-1α),transforming growth factor-β1(transforming growth factor-β1,(TGF-β1),Alpha-smooth muscle actin(α-SMA),Collagen type Ⅰ(Col Ⅰ),Collagen type Ⅲ(Col Ⅲ),tissue inhibitor of metalloproteinases 1(TIMP1),and Matrix metalloproteinases 2(MMP2).Results Compared with the control group,the model group showed significant renal function damage and fibrosis;serum BUN,SCR,and UA decreased(P＜0.05);the expression level of HIF-1α,TGF-β1,α-SMA,Col Ⅰ,Col Ⅲ,and TIMP1 protein in renal tissue increased(P＜0.05),the expression level of MMP2 and SIRT3 protein decreased(P＜0.05).Compared with the model group,the treatment group showed reduced renal function damage and fibrosis,renal function BUN,SCR,and UA content increased(P＜0.05);the expression level of HIF-1α,TGF-β1,α-SMA,Col Ⅰ,Col Ⅲ,and TIMP1 protein in renal tissue decreased(P＜0.05),the expression level of MMP2 and SIRT3 protein increased(P＜0.05).Conclusion PFD can alleviate renal function damage and fibrosis degree in rats with renal fibrosis,and its mechanism might be related to upregulation of SIRT3 protein expression.
维普
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