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Effects of prolyl 4-hydroxylase inhibitor on bladder function, bladder hypertrophy and collagen subtypes in a rat model with partial bladder outlet obstruction

机译:脯氨酰4-羟化酶抑制剂对部分膀胱出口梗阻大鼠模型膀胱功能,膀胱肥大和胶原亚型的影响

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Objective: To investigate the effects of prolyl 4-hydroxylase (P4H) inhibitor on the bladder in rats with partial bladder outlet obstruction. Methods: 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. Results: 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. Conclusion: Our data suggest that the P4H inhibitor may improve bladder function and reduce the bladder fibrosis caused by partial bladder outlet obstruction.
机译:目的:探讨脯氨酰4-羟化酶(P4H)抑制剂对部分膀胱出口梗阻大鼠膀胱的影响。方法:45只雌性Sprague-Dawley大鼠分为3组。 P4H抑制剂20 mg / kg引起的部分膀胱出口梗阻(A1,A2和A4组,每组n = 5),生理盐水引起的部分膀胱出口梗阻(B1,B2和B4组,每组n = 5)和正常控制(组C1,C2和C4,每个n = 5)。在分别在A组和B组中的部分膀胱出口阻塞1、2和4周后,以指定剂量口服抑制剂或生理盐水,每天一次,持续2周。 3、4或6周后,在膀胱测压仪检查后取出膀胱。结果:与C组相比,A组和B组的膀胱压力测量法测量的压力和体积参数以及Masson三色染色的肌肉厚度均显着高于C组(P <.05),而A组则明显低于C组。 B组(P <.05)。根据免疫组化染色和逆转录-聚合酶链反应,与C组相比,A和B组的P4H表达增加。此外,与B组相比,A组的P4H表达下降更大。与C组相比,蛋白的表达随部分膀胱出口梗阻而增加,而A组的表达则与B组相比略有下降。结论:我们的数据表明,P4H抑制剂可能改善膀胱功能并减少膀胱纤维化所致被部分膀胱出口阻塞。

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