Effect of a Prolyl 4-hydroxylase Inhibitor on Bladder Fibrosis in a Rat Model of Partial Bladder Outlet Obstruction / 대한비뇨기과학회지

ABSTRACT

PURPOSE: This study was performed to investigate prolyl 4-hydroxylase (P4H) expression changes and an inhibitor-mediated effect on bladder fibrosis in rats with partial bladder outlet obstruction(PBOO). MATERIALS AND METHODS: Twenty female Sprague-Dawley rats were divided into four groups. Group A(n=5) consisted of rats with PBOO treated with 2mg/kg P4H inhibitor, group B(n=5) consisted of rats with PBOO treated with 20mg/kg P4H inhibitor, group C(n=5) consisted of rats with PBOO treated with normal saline and group D(n=5) consisted of normal control animals. After PBOO for two weeks in the A, B, and C group rats, each amount of inhibitor was administered orally once a day for two weeks. After a total of four weeks, the bladders from all of the group rats were removed and evaluated. RESULTS: The muscle thickness calculated from Masson's trichrome staining was 0.85+/-0.22mm, 1.06+/-0.15mm, 1.19+/-0.30 and 0.49+/-0.10mm for group A, B, C, and D rats, respectively. The overall P4H expression was 65.7+/-15.2%, 13.4+/-8.4%, 73.8+/-15.5% and 10.0+/-10.0% for group A, B, C, and D rats, respectively. The overall collagen I protein expression was 16.9+/-18.0%, 17.0+/-24.1%, 30.5+/-13.4% and 8.8+/-8.7% for group A, B, C, and D rats, respectively. The overall collagen III protein expression was 9.6+/-4.2%, 8.8+/-2.9%, 12.5+/-10.6% and 7.5+/-3.5% for group A, B, C, and D rats, respectively. These results showed that PBOO led to increased muscle thickness and to an increased expression of P4H, collagen I and III protein, as compared with the group D control animals. Muscle thickness and expression of P4H, collagen I and III protein was decreased in rats treated with the P4H inhibitor-treated groups decreased as compared with rats in group C (saline-treated animals). The ratio of collagen I/III was 1.8, 1.9, 2.4 and 1.2 in group A, B, C, and D rats, respectively. CONCLUSIONS:Our results suggest that the P4H inhibitor may be potentially utilized to reduce bladder fibrosis caused by PBOO.