PDE5 抑制剂有可能改善2型糖尿病大鼠的多尿症和膀储存和排泄功能障碍
Takafumi Kabuto1, So Inamura1, Hisato Kobayashi1
1Department of Urology, Faculty of Medical Science, University of Fukui, Fukui, Japan.
PloS one
|September 18, 2024
概括
固酶-5 (PDE-5) 抑制与tadalafil改善了2型糖尿病 (T2DM) 鼠的膀功能障碍. 塔达拉菲尔治疗恢复了膀血液流动,收缩功能和减少尿动频率,这表明T2DM相关的膀问题的潜在治疗方法.
科学领域:
- 泌尿器科 泌尿器科 泌尿器科 泌尿器科
- 内分泌学 在内分泌学.
- 药理学 药理学是指药理学的学科.
背景情况:
- 2型糖尿病 (T2DM) 与膀功能障碍有关,包括储存和排泄问题.
- 膀壁的病理变化有助于这些功能障碍.
研究的目的:
- 在T2DM的老鼠模型中调查膀壁病理.
- 评估代酶-5 (PDE-5) 抑制剂塔达拉菲尔对T2DM相关的膀功能障碍的治疗效果.
主要方法:
- 使用了Otsuka Long-Evans托库希玛脂肪 (OLETF) 鼠 (T2DM模型) 和Long-Evans托库希玛Otsuka (LETO) 鼠 (对照).
- 塔达拉菲尔口服12周,评估包括排尿行为,囊泡测量,膀血流,腺三酸盐 (ATP) 释放和基因/蛋白质表达 (VNUT,缺氧标志物,细胞因子,生长因子).
- 膀条纹测试评估了收缩反应.
主要成果:
- T2DM大鼠表现出增加的排尿频率,尿量和非排泄的收缩,以及膀血流减少和ATP释放增加,并具有更高的VNUT表达.
- 塔达拉菲尔的使用抑制了这些与T2DM相关的变化,包括减少HIF-1α,8-OHdG,IL-6,TNF-α,IGF-1和bFGF的表达.
- 在T2DM大鼠中,失效的膀收缩反应被tadalafil恢复.
结论:
- T2DM大鼠表现出多尿症,由于膀血液流量减少而增加ATP释放,膀收缩能力受损.
- 通过塔达拉菲尔抑制PDE-5改善了这些病理变化.
- 塔达拉菲尔可能为与T2DM相关的尿频和膀储存/排泄功能障碍提供预防策略.
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