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    Korean J Urol. 2008 Mar;49(3):227-236. Korean.
    Published online Mar 31, 2008.
    https://doi.org/10.4111/kju.2008.49.3.227
    Copyright © 2008 The Korean Urological Association
    Original Article

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

    Jae Min Chung,1 Dong Gil Shin,2 Min Jung Jung,3 Sang Don Lee,4,5 and Jeong Zoo Lee4,5
      • 1Department of Urology, College of Medicine, Kosin University, Korea.
      • 2Department of Urology, Moonhwa Hospital, Pusan National University, Busan, Korea.
      • 3Department of Pathology, College of Medicine, Kosin University, Korea.
      • 4Department of Urology, College of Medicine, Pusan National University, Busan, Korea.
      • 5Medical Research Institute, Pusan National University, Busan, Korea.
    Received January 14, 2008; Accepted February 04, 2008.

    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.

    Keywords
    Bladder; Obstruction; Rats; Prolyl 4-hydroxylase inhibitor

    Figures

    Fig. 1
    Partial bladder outlet obstruction model in rats. (A) Through a lower transverse incision, the middle urethra was exposed. (B) One surgeon consistently ligated around the urethra with 4/0 silk in the presence of an intraluminally placed medicut catheter with a steel rod and extraluminally placed medicut catheter without a steel rod.

    Fig. 2
    Muscle thickness (Masson's trichrome staining, x40). (Group A) Partial bladder outlet obstruction (PBOO) in rats treated with 2 mg/kg prolyl 4-hydroxylase (P4H) inhibitor, (Group B) PBOO in rats treated with 20mg/kg P4H inhibitor, (Group C) PBOO in rats treated with normal saline, (Group D) normal control rats.

    Fig. 3
    Prolyl 4-hydroxylase (P4H) expression (immunohistochemical staining, x400). (Group A) partial bladder outlet obstruction (PBOO) in rats treated with 2mg/kg P4H inhibitor, (Group B) PBOO in rats treated with 20mg/kg P4H inhibitor, (Group C) PBOO in rats treated with normal saline, (Group D) normal control rats.

    Fig. 4
    Collagen I expression (immunohistochemical staining, x400). (Group A) partial bladder outlet obstruction (PBOO) in rats treated with 2mg/kg P4H inhibitor, (Group B) PBOO in rats treated with 20mg/kg P4H inhibitor, (Group C) PBOO in rats treated with normal saline, (Group D) normal control rats.

    Fig. 5
    Collagen III expression (immunohistochemical staining, x400). (Group A) partial bladder outlet obstruction (PBOO) in rats treated with 2mg/kg P4H inhibitor, (Group B) PBOO in rats treated with 20mg/kg P4H inhibitor, (Group C) PBOO in rats treated with normal saline, (Group D) normal control rats.

    Tables

    Table 1
    Data summary of muscle thickness, P4H, collagen I and III

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    MeSH Terms
    Animals
    Collagen
    Female
    Fibrosis
    Humans
    Muscles
    Procollagen-Proline Dioxygenase
    Rats
    Rats, Sprague-Dawley
    Urinary Bladder
    Urinary Bladder Neck Obstruction
    Metrics
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