Effect Of Qihong Tongyu Decoction On Wnt/β-catenin Signaling Pathway In Renal Tissue Of Rats With Renal Interstitial Fibrosis

Objective:This experiment was to observe the effect and mechanism of Qihong Tongyu Decoction on Wnt/β-catenin signaling pathway of renal tissue in rats induced by unilateral ureteral obstruction（UUO）.Methods:At first,60 male Sprague-Dawley（SD）rats were randomly divided into sham operation group,model group,Qihong Tongyu Decoction low-dose group,Qihong Tongyu Decoction middle-dose group,Qihong Tongyu Decoction high-dose group and enalapril group.The model of unilateral ureteral obstruction was established in each group.On the 8th day after the model was made,each group was given related drug therapy:The concentrations of Qihong Tongyu Decoction in low-dose group,middle-dose group and high-dose group were respectively 1.3g·mL^-1,2.6g·mL^-1,5.2g·mL^-1;The enalapril group was 0.94g·mL^-1,the sham operation group and the model group were given the same volume of 0.9%sodium chloride solution,and the morning and the evening were given the same volume of 1mL,the intervention time was 14 day.Take blood and kidney after 14 days.Serum creatinine（Scr）and urea nitrogen（Bun）were detected in each group.HE staining and Masson staining were used to observe the pathological changes of renal tissues.The expression of transforming growth factor-β1（TGF-β1）and fibronectin（FN）protein was detected by immunohistochemical method.And wnt1,β-catenin protein and its mRNA expression were detected in renal tissues by western Blot and Real time fluorescence PCR.Results:1.Renal function evaluation index:Compared with the sham operation group,the Scr and BUN of the other groups were significantly increased（P<0.05）.Compared with the model group,there was no significant difference in SCR and BUN in the low-dose group of Qihong Tongyu decoction（P>0.05）,while the SCR and BUN in the middle and high-dose group of Qihong Tongyu Decoction and the enalapril group was significantly decreased（P<0.05）.However,there was no significant difference between the high-dose group of Qihong Tongyu Decoction and enalapril group（P>0.05）.Pathological results of renal tissue:the structure of renal tissue in sham operation group was normal.A small amount of blue collagen fibers were deposited in the renal tissue of the sham operation group.However,in the model group,the renal tissue structure was disordered,the official cavity of the renal tubule was obviously dilated,the arrangement was sparse,the interstitial of the renal tubule was obviously widened,the inflammatory cells infiltrated in the interstitium,and a large amount of blue collagen fibers were deposited.The lesions of Qihong Tongyu Decoction group and enalapril group were less than those of model group,but they were still more serious than those of sham operation group.2.The results of immunohistochemical method:The positive expression of sham operation group was weak,only a small amount of brown granules were found in the interstitium.The positive expression in the model group was very strong,and there were a large number of brownish-yellow granules in the tubules,glomeruli and tubules.The positive expression of Qihong Tongyu Decoction in each dose group and enalapril group was between sham operation group and model group.That is,compared with the sham operation group,the expression of TGF-β1 and FN protein in the model group was significantly increased（P<0.05）.Compared with the model group,the expression of TGF-β1 and FN protein in the traditional chinese medicine Qihong Tongyu Decoction group and the enalapril group were significantly decreased（P<0.05）.Among them,Qihong Tongyu Decoction group showed a dose-dependence decrease;There was no significant difference in the expression of TGF-β1 and FN protein between the enalapril group and the high dose group of traditional Chinese medicine.4.Western Blot and Real time fluorescence PCR showed:The expression of Wnt1,β-catenin protein and mRNA were increased in the rat kidney in the model group（P<0.05）.The expression of Wnt1,β-catenin protein and mRNA in Qihong Tongyu Decoction group decreased in dose-dependent manner.There was no significant difference between the enalapril group and the Chinese medicine high dose group（P>0.05）Conclusion:1.Qihong Tongyu Decoction can reduce BUN and Scr in UUO rats,and improve the pathological changes of renal interstitial fibrosis.The suggests that Qihong Tongyu Decoction has the effect of inhibiting renal interstitial fibrosis.2.Qihong Tongyu Decoction can reduce the expression ofβ-catenin,wnt1protein and its mRNA in wnt/β-catenin signaling pathway.This suggests that Qihong Tongyu Decoction may inhibit the activation of Wnt/β-catenin signaling pathway,thereby inhibiting renal interstitial fibrosis.