The Effect Of Formononetin On The Mechanisms Of ASK1-JNK Pathway In Rats With Renal Interstitial Fibrosis

Renal fibrosis is the main pathological and common pathway leading to renal failure in a variety of chronic kidney diseases.Recent studies have shown that ASK-JNK pathway is involved in the occurrence of renal interstitial fibrosis is an important pathway of apoptosis.Formononetin is able to resist apoptosis and protect the kidneys.Therefore,this study explored the effects of formononetin on renal interstitial fibrosis in rats and its influence on the biological pathway of ASK1-JNK,in order to find a key target for the treatment of renal interstitial fibrosis and formononetin The intervention provides new ideas.(1)Intervention of formononetin on rats with renal fibrosisAn animal model of renal interstitial fibrosis in rats was established by unilateral ureteral obstruction.Compared with the sham operation group,the renal function of the model group was consistent with the clinical manifestations,and the serum Scr and BUN were significantly increased(P<0.01).The left kidney was visually observed to increase the volume of the kidney and showed obvious effusion.The boundary between the cortex and medulla was unclear,and the renal weight index was significantly increased(P<0.01).The hepatic epithelial cell arrangement was observed by hematoxylin-eosin staining.There was no disorder and the renal tubular injury index increased significantly(P<0.01).Masson staining showed a large amount of fibrillar collagen proliferation in renal tissue;the relative area of renal interstitial collagen was significantly increased(P<0.01).Compared with the model group,Scr and BUN were significantly decreased in each dose group of formononetin and enalapril.The degree of hydronephrosis in the left kidney was reduced,and the renal weight index was significantly reduced;the renal tubules were slightly dilated,the renal interstitial edema was mild,and the renal tubular injury index was decreased;the collagen fibers and interstitial collagen fibers were relatively less expressed,and the kidneys were relatively The relative area of collagen decreased signifieantly.There was a statistieally significant differenee between the high dose group of formononetin and the enalapril group(P<0.05).(2)Regulation mechanism of formononetin on ASK 1-JNK pathway in rats with renal fibrosisDuring the progression of interstitial fibrosis,the degree of renal fibrosis was positively correlated with the number of apoptosis of renal tubular epithelial cells.The more the number of apoptosis,the more severe the degree of fibrosis.Studies have shown that ASK1 and JNK are important proteins in the process of apoptosis.Therefore,this part first uses Western blotting to investigate the effect of formononetin on the expression of ASK1 and JNK proteins in renal tissues.The results showed that the expression of ASK1 and JNK protein was significantly increased in the model group compared with the sham operation group(P<0.01).Compared with the model group,the treatment group could decrease the expression of ASK1 and JNK protein in renal tissue(P<0.05,P<0.01).There was a statistical difference(P<0.05)between the high dose group of formononetin and the enalapril group.The effect of the formononetin on the apoptosis of renal tubular epithelial cells was investigated by Tunel method.Compared with the sham operation group,the apoptotic renal tubular epithelial cells were significantly increased in the model group(P<0.01).Compared with the model group,the apoptosis index of each treatment group was significantly decreased(P<0.05,P<0.01);The apoptotic index was significantly lower in the high-dose group compared with the enalapril group.(P<0.05).Conclusion:Formononetin can protect the renal function of rats with RIF;alleviate the condition of hydronephrosis in the affected kidney;and reduce the interstitial fibrosis,vacuolar degeneration of renal tubular epithelial cells,and interstitial infiltration in UUO rats.In order to reduce renal tubulointerstitial injury;to reduce the synthesis of interstitial collagen fibers in rat kidney,the excessive deposition of extracellular matrix has improved,impeding the development of renal interstitial fibrosis;and interfering with the expression of ASK1 and JNK proteins,thereby inhibiting The apoptosis pathway mediated by ASK1-JNK pathway prevents renal interstitial fibrosis caused by apoptosis of renal tubular epithelial cells.