| Objective: To explore the expression changes and the roles of bone morphorgenetic protein-7 (BMP-7) and its receptors (BMPR- Ⅱ, ALK-2, ALK-3, ALK-6) in the renal tubulo-interstitial lesions induced by unilateral ureteral obstruction (UUO) and investigate the effect and mechanism of Yanshen Capsule on the renal fibrosis.Methods: A total of 80 healthy male rats were randomly divided into four groups: normal control group rats did not receive any operation or treatment; sham operation group rats just received an operation without ureteral obstruction and were gavaged with saline daily; UUO group rats received an operation with left ureteral obstruction below the renal pelvis and were also gavaged with saline daily; Yanshen capsule treated group rats received an operation with left ureteral obstruction below the renal pelvis and were gavaged with Yanshen Capsule daily. At postoperative day 1,3,7,14, five rats in each group were sacrificed and the left kidneys were removed to perform the further study. The protein expression site and level of BMP-7 , TGF- β and α -SMA was detected by immunohistochemistry staining. The mRNA level of BMP-7, BMPR- Ⅱ, ALK-2, ALK-3 and ALK-6 was examined by RT-PCR.Results: Along with the delay of the ureteral obstructed days, the lesions of renal tissue were more and more serious. At the 14th postoperated day, typical renal interstitial fibrosis formed. Immunohistochemistry staining studies indicated that in normal rat kidneys BMP-7 mainly expressed in renal tubular and interstitial, rarely in glomeruli. BMP-7-positive staining was found in some but not all cortical proximal tubular cross-sections and more intensively in straight portions in the cortico-medullary junction. Distal convoluted tubules were stained strongly, as were collecting ducts. And in UUO rats, the protein expression of BMP-7 significantly decreased, but the expression of TGF-β1 and α-SMA significantly increased according to the obstructed days. The renal tubulointerstital expression of BMP-7 was significantly negatively associated with the expression of TGF-β1and a-SMA. We also found that the protein expression of BMP-7 was higher, but the expression of TGF-p\ and a-SMA was lower to some extent in the Yanshen Capsule-treated group rats than the same time point rats in UUO group. The RT-PCR results showed that the mRNA level of BMP-7, BMPR- II, ALK-2, ALK-3 and ALK-6 was high in control group rats. And compared to sham operation groups, the mRNA level of BMP-7, BMPR- II, ALK-2 and ALK-3 was significantly decreased, but the change of ALK-6 mRNA was not marked in UUO rats. We also found that the mRNA expression of BMP-7 and its receptors was higher to some extent in the Yanshen Capsule-treated group rats than the same time point rats in UUO group.Conclusion: (l)In normal kidneys the expression of BMP-7 and its receptors was abundant. And BMP-7 mainly expressed in renal tubular and interstitial, rarely in glomeruli. The expression in medullary was higher than cortical area. (2)The loss of BMP-7 and its receptors (BMPR- II, ALK-2, ALK-3) was explored in the early phase of fibrotic process, ahead of the pathologic changes in the kidney, and might play a very important role in mediating the renal tubulointerstital fibrosis. (3) Yanshen Capsule could delay the progression of renal interstitial fibrotic disease through increasing BMP-7 expression and suppressing TGF-(3i and a-SMA expression.
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