The Impact Of Jiaweiliuweidihuang Decoction On The Wnt4/β-catenin Pathway Regulated Fibroblast Growth Factor-23 In The Rat Kidney Tissue With Unilateral Ureteral Obstruction

Objective: The regulation of FGF-23 through Wnt4/β-catenin pathway activation was regarded as the entry point,this paper aims to explore if UUO rat model has activation of kidney tissue Wnt4/β-catenin pathway,further regulate expression of FGF-23 and get involved in the development of renal interstitial fibrosis(RIF)through the UUO rat model.It also explores whether RIF action mechanism of jiaweiliuweidihuang decoction blocks the regulation and activation of Wnt4/β-catenin pathway or if it is related to the expression of FGF-23.Methods: It adopts 75 SD male rats and randomly divides them into five groups based on weight: normal group(n=15),sham group(n=15),model group(n=15),Chinese medicine group(n=15)and valsartan group(n=15).Each group also randomly divides three time points,7 days,14 days and 28 days.Each time point puts five rats into death,while normal group implements one-time execution when the experiment is done.Normal group and sham group give normal saline(2ml/a rat /d)gavage every day;Chinese medicine group gives preparative jiaweiliuweidihuang decoction(2ml/a rat /d)gavage;valsartan group gives valsartan(30mg/kg/d)gavage.And left kidney for inspection.Kidney tissue implements HE staining and Masson staining.Observe the change in renal pathology under the optical microscope andcarry out semi-quantitative scoring system.Apply immunohistochemical method and western blot to test the expression of Wnt4,β-catenin and FGF-23 protein in kidney tissue.Result: 1.Pathological result shows that rats in the normal group and sham operation group have normal glomerulus,renal tubule and interstitium.Kidney tissue of rats in model group has pathologic changes in tubular atrophy,interstitial fibrosis and interstitial inflammatory cell infiltration on the 7th day.The pathology deteriorates and reaches to the peak on the 14 th day with the extension of obstruction duration.Interfered by jiaweiliuweidihuang decoction and valsartan,tubular atrophy,interstitial fibrosis and interstitial inflammatory cell infiltration are improved.The result of semi-quantitative scoring shows that compared to the semi-quantitative scoring in the sham group at the same time on the 7th day,14 th day and 28 th day,semi-quantitative scoring in the model group rises at each time point,and the difference is statistically significant(p < 0.01),while the rats’ semi-quantitative scoring in the Chinese medicine group and valsartan group drops on the 7th day,14 th day and 28 th day,and differences are statistically significant compared to the same time point of model group(p<0.01).2.According to the result of immunohistochemical method,a small quantity of expressions of Wnt4,β-catenin and FGF-23 positive protein are shown in rats’ renal tubule and interstitium,while the increase of Wnt4,β-catenin and FGF-23 positive protein staining can be seen in renal tubule and interstitium in the model group on the 14 th day.However,through the treatment of jiaweiliuweidihuang decoction and valsartan,Wnt4,β-catenin and FGF-23 positive protein staining of tubule and interstitium alleviates on the 7th day.According to the result of western blot,expression of Wnt4,β-catenin and FGF-23 protein in rats’ kidney tissue in the model grouprises on the 7th day,14 th day and 28 th day compared to that of sham group,and the difference is statistically significant(p<0.01).Expression of Wnt4,β-catenin and FGF-23 protein in rats’ kidney tissue in the Chinese medicine and valsartan group drops on the 7th day,14 th day and 28 th day,and differences are statistically significant(p<0.01)compared to that of model group in the same time.Conclusion: 1.Jiaweiliuweidihuang decoction is able to lower UUO rat’s serum BUN and Scr,improve RIF pathology and reflect that it has the effect of anti-RIF.2.The up-regulation of Wnt4,β-catenin and FGF-23 protein in UUO rat’s kidney tissue shows that Wnt4/β-catenin pathway revitalizes and FGF-23 might be involved in the RIF process.3.Jiaweiliuweidihuang decoction can reduce the expression of FGF-23,Wnt4 andβ-catenin protein of UUO rat model,which represents that its mechanism of anti-RIF might be related to the suppression of activation of Wnt4/β-catenin pathway and the expression of FGF-23.