Korean J Urol.  2008 Mar;49(3):227-236. 10.4111/kju.2008.49.3.227.

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

• Chung JM
• Shin DG
• Jung MJ
• Lee SD
• Lee JZ

• KMID: 1204624
• DOI: http://doi.org/10.4111/kju.2008.49.3.227

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.

Keyword

Bladder; Obstruction; Rats; Prolyl 4-hydroxylase inhibitor

MeSH Terms

Female
Humans
Rats
Animals

Figure

• 

  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.

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  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.

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  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.

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  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.

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  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.

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