Department of Urology, Kosin University College of Medicine, Busan, Korea.
Urology. 2012 Dec;80(6):1390.e7-12. doi: 10.1016/j.urology.2012.07.019. Epub 2012 Sep 15.
To investigate the effects of prolyl 4-hydroxylase (P4H) inhibitor on the bladder in rats with partial bladder outlet obstruction.
Forty-five female Sprague-Dawley rats were divided into 3 groups; partial bladder outlet obstruction with P4H inhibitor 20 mg/kg (groups A1, A2, and A4, each n = 5), partial bladder outlet obstruction with normal saline (groups B1, B2, and B4, each n = 5), and normal control (groups C1, C2, and C4, each n = 5). After partial bladder outlet obstruction for 1, 2, and 4 weeks in the groups A and B, respectively, the inhibitor or normal saline were administered orally at the indicated dosage once a day for 2 weeks. After either 3, 4, or 6 weeks, the bladders were removed after cystometry.
The pressure and volume parameters from the cystometry and the muscle thickness from the Masson trichrome staining of groups A and B increased significantly compared to those in group C (P < .05), and those in group A were significantly lower than those of group B (P < .05). Based on immunohistochemical staining and reverse transcription-polymerase chain reaction, P4H expression in groups A and B was increased compared with that in group C. Furthermore, P4H expression showed a larger decrease in group A compared to that in group B. Collagens I and III protein expressions increased with partial bladder outlet obstruction in comparison with that of group C, and expression in group A was marginally decreased compared with expression in group B.
Our data suggest that the P4H inhibitor may improve bladder function and reduce the bladder fibrosis caused by partial bladder outlet obstruction.
探讨脯氨酰 4-羟化酶(P4H)抑制剂对大鼠部分膀胱出口梗阻模型膀胱的作用。
45 只雌性 Sprague-Dawley 大鼠分为 3 组;分别给予 P4H 抑制剂 20mg/kg(A1、A2、A4 组,每组 n=5)、生理盐水(B1、B2、B4 组,每组 n=5)和正常对照组(C1、C2、C4 组,每组 n=5)。分别在 A、B 组大鼠进行部分膀胱出口梗阻 1、2、4 周后,每天口服相应剂量的抑制剂或生理盐水 2 周。分别在 3、4、6 周后,进行膀胱测压并取出膀胱。
与 C 组相比,A、B 组大鼠的膀胱测压压力和容积参数以及 Masson 三色染色的肌肉厚度明显增加(P<0.05),A 组明显低于 B 组(P<0.05)。免疫组化染色和逆转录-聚合酶链反应显示,A、B 组 P4H 表达较 C 组增加,A 组 P4H 表达较 B 组降低。与 C 组相比,I 型和 III 型胶原蛋白表达在部分膀胱出口梗阻时增加,A 组的表达与 B 组相比略有下降。
P4H 抑制剂可改善膀胱功能,减轻部分膀胱出口梗阻引起的膀胱纤维化。