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羊水干细胞改善大鼠慢性膀胱缺血引起的膀胱功能障碍。

Amniotic fluid stem cells ameliorate bladder dysfunction induced by chronic bladder ischemia in rat.

机构信息

Female Urology Section, Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital Linkou Medical, Taoyuan, Taiwan.

College of Medicine, Chang Gung University, Taoyuan, Taiwan.

出版信息

Neurourol Urodyn. 2018 Jan;37(1):123-131. doi: 10.1002/nau.23316. Epub 2017 Jun 12.

Abstract

AIMS

This study investigated the protective effect of human amniotic fluid-derived stem cells (hAFSCs) against bladder overactivity in rat model of atherosclerosis-induced chronic bladder ischemia.

METHODS

Adult female Sprague-Dawley rats were divided into six groups: (1) Normal control with a regular diet for 8 weeks, (2) Sham-operation, (3) arterial balloon endothelial injury (AEI) of common iliac artery (AEI only), and post-AEI consecutive hAFSCs treatment for (4) 1 day, (5) 3 days, and (6) 7 days. Groups 2-6 were given 2% cholesterol diet for 8 weeks after operation (sham or AEI). Bladder functions were analyzed by cystometry at 8 weeks in controls and after operation in groups 2-6. Wall morphology of common iliac artery was examined by hematoxylin and eosin stain. Bladder oxidative stress and inflammatory markers were studied by immunohistochemistry of 8-hydroxy-2'-deoxyguanosine (8OHdG), malondialdehyde (MDA), and tumor necrosis factor-alpha (TNF-alpha).

RESULTS

Bladder overactivity with decreased voided volumes and intercontraction intervals and increased residual volumes was seen in AEI only group, but improved after hAFSCs treatment for 1, 3, and 7 days. Compared with controls and shams, the wall thickness of iliac artery was increased in AEI only group, but improved after hAFSCs treatment for 3 and 7 days. The expressions of 8OHdG, MDA, and TNF-alpha were increased in AEI only group, but improved after hAFSCs treatment for 1, 3, and 7 days.

CONCLUSIONS

Bladder overactivity caused by chronic bladder ischemia can be improved by hAFSCs treatment, probably by acting through down-regulation of oxidative stress and TNF-alpha expressions.

摘要

目的

本研究旨在探讨人羊膜间充质干细胞(hAFSCs)对动脉粥样硬化诱导的慢性膀胱缺血大鼠模型中膀胱过度活动的保护作用。

方法

成年雌性 Sprague-Dawley 大鼠分为六组:(1)正常对照组,给予常规饮食 8 周;(2)假手术组;(3)髂总动脉球囊内皮损伤(AEI)组,仅行手术;(4)AEI 后连续给予 hAFSCs 治疗 1 天组;(5)AEI 后连续给予 hAFSCs 治疗 3 天组;(6)AEI 后连续给予 hAFSCs 治疗 7 天组。术后 2-6 组给予 2%胆固醇饮食 8 周。对照组在 8 周时进行膀胱功能分析,2-6 组在术后进行膀胱功能分析。苏木精和伊红染色观察髂总动脉壁形态。免疫组化检测 8-羟基-2'-脱氧鸟苷(8OHdG)、丙二醛(MDA)和肿瘤坏死因子-α(TNF-α)研究膀胱氧化应激和炎症标志物。

结果

AEI 组出现膀胱过度活动,表现为排尿量和两次收缩间隔减少,残余尿量增加,但 hAFSCs 治疗 1、3 和 7 天后得到改善。与对照组和假手术组相比,AEI 组髂总动脉壁厚度增加,但 hAFSCs 治疗 3 和 7 天后得到改善。AEI 组 8OHdG、MDA 和 TNF-α表达增加,但 hAFSCs 治疗 1、3 和 7 天后得到改善。

结论

慢性膀胱缺血引起的膀胱过度活动可通过 hAFSCs 治疗得到改善,可能通过下调氧化应激和 TNF-α表达来实现。

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