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缝隙连接抑制剂对膀胱出口梗阻诱导的逼尿肌过度活动的治疗作用。

Therapeutic effects of connexin inhibitors on detrusor overactivity induced by bladder outlet obstruction in rats.

机构信息

Department of Urology, College of Medicine, The Catholic University of Korea, Seoul, Korea.

出版信息

Urology. 2011 Aug;78(2):475.e1-7. doi: 10.1016/j.urology.2011.03.029.

DOI:10.1016/j.urology.2011.03.029
PMID:21820587
Abstract

OBJECTIVES

To investigate the alterations in Connexin 43 (Cx43) and connexin 26 (Cx26) levels in the bladder outlet obstruction (BOO)-induced detrusor overactivity and examine the effect of connexin inhibitors on this condition.

METHODS

Fifty Sprague-Dawley rats were divided into 4 groups: sham-operated control group (n = 10), BOO group (n = 10), and 2 groups that were administered connexin inhibitors. The first of these 2 groups was administered 18β-glycyrrhetinic acid (BOO-18β-GA group, n = 15) and the second group was given oleamide (BOO-oleamide group, n = 15). Cystometrogram was performed in all groups after 2 weeks of obstruction. The expression levels of Cx26 and Cx43 were analyzed using immunohistochemical staining and Western blot.

RESULTS

The intercontraction interval was markedly shorter in the BOO group compared with the control group (P <.05). Intercontraction intervals in the BOO-18β-GA and BOO-oleamide groups at 2 weeks were significantly longer than that observed for the BOO group (P <.05). The expression of Cx43 and Cx26 were increased in the BOO group. After administration of connexin inhibitors, downregulation of Cx43 and Cx26 was noted.

CONCLUSIONS

These results suggest that upregulation of Cx43 and Cx26 induce detrusor overactivity after BOO, and connexin inhibitors may have some role in relieving BOO-induced detrusor overactivity in rats.

摘要

目的

研究缝隙连接蛋白 43(Cx43)和缝隙连接蛋白 26(Cx26)在膀胱出口梗阻(BOO)诱导的逼尿肌过度活动中的变化,并观察缝隙连接抑制剂对此情况的影响。

方法

将 50 只 Sprague-Dawley 大鼠分为 4 组:假手术对照组(n = 10)、BOO 组(n = 10)和 2 组接受缝隙连接抑制剂的治疗组。其中一组给予 18β-甘草次酸(BOO-18β-GA 组,n = 15),另一组给予油酸酰胺(BOO-油酸酰胺组,n = 15)。所有组在梗阻 2 周后进行膀胱测压。采用免疫组织化学染色和 Western blot 分析 Cx26 和 Cx43 的表达水平。

结果

与对照组相比,BOO 组的收缩间期明显缩短(P <.05)。BOO-18β-GA 组和 BOO-油酸酰胺组在 2 周时的收缩间期明显长于 BOO 组(P <.05)。Cx43 和 Cx26 的表达在 BOO 组中增加。给予缝隙连接抑制剂后,Cx43 和 Cx26 的表达下调。

结论

这些结果表明,Cx43 和 Cx26 的上调在 BOO 后引起逼尿肌过度活动,缝隙连接抑制剂可能在缓解大鼠 BOO 引起的逼尿肌过度活动方面具有一定作用。

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