Effect And Mechanism Of Modified Dahuang Zhechong Pill On Renal Interstitial Fibrosis In Rats With Obstructive Nephropathy

Objective:To explore the effect and mechanism of modified Dahuang Zhechong Pill on renal interstitial fibrosis in rats with obstructive nephropathy.Methods:Using a unilateral ureteral ligation(UUO)-induced renal interstitial fibrosis model,50 SD rats were randomly divided into 5 groups:sham operation group(Sham group,normal saline 2 m L),model group(UUO group,normal saline 2 mL),low dose treatment group of modified Dahuang Zhechong Pill(9.5g·kg-1),high dose treatment group of modified Dahuang Zhechong Pill(1 9g·kg-1),enalapril group(0.001 g·kg-1).On the 1 5th day after operation,the rats in each group were sacrificed and blood was collected.The levels of serum creatinine(Scr)and urea nitrogen(BUN)were determined by enzymatic method.The urine was collected for 24 hours.The urinary protein content was determined by the method of pyrogallol red molybdenum end point method.The ligation-side renal tissues were stained with hematoxylin-eosin(H E)and Masson;the expression of transforming growth factor-?1(TG F-?1),fibronectin(FN)and a-smooth actin(a-SMA)were determined by immunohistochemistry.Expression of TG F-?1,p38 mitogen-activated protein kinase(p38MAPK)and phosphorylated p38MAPK(p-p38MAPK)were detected in Western-blot.Results:Compared with the sham operation group,the amount of 24h-Upro,Scr and BUN in the model group was significantly increased(P<0.01).Under the light microscope,the renal tubules of the model group were severely dilated,and the epithelial cells were flat and detached.More epithelial cells were vacuolated,part of tubular were atrophy,renal interstitium were fibrosis and dropsical.Inflammatory cells were infiltration,such as lymphocytes and monocytes.a large number of collagen fibers stained blue in the renal tubules and renal interstitial,distributed in bundles,reticular,tubular dilatation,and partial tubular were atrophy;renal pathological score of renal inj u ry in UUO group was significantly increased(P<0.01);renal collagen volume was significantly increased(P<0.01);TG F-(31,FN,a-SMA High(P<0.05);TG F-(31,p38,p-p38 increased in Western-Blot(P<0.05);compared with UUO group:24h-Upro,Scr,BUN decreased in each drug group(P<0.05),kidney Tissue damage was alleviated,but it was still heavier than Sham group.The pathological scores of each group were significantly lower(P<0.05),renal collagen volume was significantly decreased(P<0.05),and TG F-?1,FN and a-SMA were decreased(P<0.05),TG F-(31,p-p38 decreased in Western-Blot(P<0.05),no difference in p38;rhubarb Expression of the indicators of the size of dose pill bug dose dependent decrease;Comparative indicators medicine group and high dose group no significant difference(P>0.05).Conclusion:Modified Dahuang Zhechong Pill may improve renal interstitial fibrosis by reducing the high expression of FN and a-SMA,down-regulating the expression of p-p38MAPK and TGF-?1 in p38MAPK signaling pathway,reducing extracellular matrix over deposition and renal cell damage.