Expression Of Cathepsin B In The 5/6 Nephrectomized Rat Remnant Kidney And The Effects Of Yanshen Capsule Interference

Objective: To study the expression of cathepsin B (CB) in the 5/6 nephrectomized rat remnant kidneyï¼›to investigate the effects of Yanshen Capsule on the remnant kidney and the related mechanism.Methods: 120 healthy Wistar rats were randomly divided into 3 groups with 40 animals in each group. Rats in control group were sham-operated and gavaged with saline daily, rats in operation group were 5/6 nephrectomized and gavaged with saline daily, rats in treatment group were 5/6 nephrectomized followed by gavaging with Yanshen Capsule daily. 10 rats were killed on postoperative 15d, 30d, 60d, 90d respectively in each group . The Body weight(BW), urine protein, blood urea nitrogen(BUN) and creatinine (SCr) levels were determined .Renal morphological changes were observed .The expression of collagen â…£(Col â…£) and cathepsin B were investingated by using immunohistochemistry and RT-PCR.Results: The levels of BUN, SCr and urine protein in operation group were increased on 15th day, and were decreased on 30th day, and then increased on 60th until 90th day after operation, Compared with sham control group, the levels of BUN, SCr and urine protein in operation group were all significantly increased. The BUN, SCr and urine protein in Yanshen Capsule-treated group were slightly higher than those in control group, but were significantly lower than those in operation group(p<0.01). In operation group, glomerular hypertrophy, mesangial hyperplasia and extension, glomerulosclerosis, renal tubular dilataltion, protein cast, mononuclear inflammatory cell infiltration and fibrosis in renal interstitial, higher expression of Col â…£, higher ratio of sclerosis glomeruli and damaged tubuli and interstitial were observed 30 days after operation. These changes became progressively severer from 60 days to 90 days after operation. In Yanshen Capsule-treated group these changes were less remarkable when compared to the operation group. The CB was mainly expressed in proximal convoluted tubular epithelial cells and was less in golmerulus, distal convoluted tubule and collecting duct. In operation group, the expression of CB mRNA and protein were elevated on 15th day and 30th day after operation, and decreased gradually on 60th day and 90th day after operation. The CB expression in YanshenCapsule-treated group was significantly higher than that of operation group. The expression of renal Col â…£ was positively correlated with the ratio of sclerosis glomeruli and percentage of damaged tubulointerstitial, while the expression of renal CB was negatively correlated with the ratio of sclerosis glomeruli, damaged tubulointerstitial, and renal Col â…£.Conclusions: (1) The CB was mainly expressed in proximal convoluted tubular epithelial cells. (2) In the early period after operation, renal CB expression was increased in 5/6 nephrectomized rats, then gradually decressed.The changes of renal CB during the late stage of the experiment might contribute to the ECM accumulation and renal fibrosis. (3) Yanshen Capsule could delay the development of renal fibrosis through increasing CB and suppressing Col â…£ expression.