Antagonizing effects of Shenkang Injection on renal interstitial fibrosis in model rat of chronic aristolochic acid nephropathy

Objective To study the antagonizing effects of Shenkang Injection(SKI) on renal interstitial fibrosis in model rats with chronic aristolochic acid nephropathy(CAAN).Methods Eighteen male SD rats were equally divided into the following three groups: control group,model gruop,and intervention group.Body weight,urinary glucose,24 h urinary protein excretion,and creatinine clearance(Ccr) were measured at the end of 0,1,4,8,and 12 week,respectively.At the end of the 12 week,all the rats were sacrificed and the renal pathological examination of each rat was performed.The mRNA and protein expression of transforming growth factor-β1(TGF-β1),connective tissue growth factor(CTGF),plasminogen activator inhibitor-1(PAI-1),tissue inhibitor of metalloproteinase-1(TIMP-1),and type I collagen(Col I) in kidney tissue were determined by realtime(RT)-PCR and immunohistochemistry staining,respectively.Results Compared with control group,body weight of rats in intervention group and intervention group were significantly decreased(P0.01);body weight of rats in intervention group was higher than that in intervention group,with a significant difference at the end of 12 week(P0.05).Compared with control group,the 24 h urinary protein excretion of rats in model group and intervention group increased significantly(P0.01);but the 24 h urinary protein excretion of rats in intervention group was lower than that in model group(P0.05).Compared with control group,the Ccr of model rats decreased significantly(P0.01);the Ccr of rats in intervention group was significantly higher than that in model group(P0.01).Compared with control group,the relative area of interstitial fibrosis of kidney tissue,in model rats was significantly enlarged(P0.01).The mRNA and protein expression of TGF-β1,CTGF,PAI-1,TIMP-1,Col I in kidney tissue was significantly up-regulated(P0.01) in the model rats.Compared with the control group.The increased mRNA and protein expression of TGF-β,CTGF,PAI-1,TIMP-1,Col I were all significantly down-regulated in intervention group(P0.05).Conclusion SKI could inhibit the production of promoting extracellular matrix(ECM) synthesis factors(TGF-β1 and CTGF) and antagonizing ECM degradation factors(TIMP-1 and PAI-1) in kidney tissue,which might be the mechanism that SKI alleviates the renal interstitial fibrosis and improves the renal function in CAAN rats.