[1]李佳,夏六兵,张腾,等.4-PBA抑制内质网应激降低间质性膀胱炎大鼠膀胱兴奋性[J].第三军医大学学报,2016,38(11):1270-1275.
 Li Jia,Xia Liubing,Zhang Teng,et al.4-PBA inhibits endoplasmic reticulum stress to down-regulate bladder excitation in protamine/lipopolysaccharide-induced interstitial cystitis in rats[J].J Third Mil Med Univ,2016,38(11):1270-1275.
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《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
38卷
期数:
2016年第11期
页码:
1270-1275
栏目:
基础医学
出版日期:
2016-06-15

文章信息/Info

Title:
4-PBA inhibits endoplasmic reticulum stress to down-regulate bladder excitation in protamine/lipopolysaccharide-induced interstitial cystitis in rats
作者:
李佳夏六兵张腾董兴有宋波李龙坤
第三军医大学新桥医院泌尿外科; 第三军医大学西南医院全军泌尿外科研究所
Author(s):
Li Jia Xia Liubing Zhang Teng Dong Xingyou Song Bo Li Longkun

Department of Urology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037; Institute of Urinary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China

关键词:
内质网应激自噬流间质性膀胱炎4-PBA
Keywords:
endoplasmic reticulum stress autophagy flux interstitial cystitis 4-PBA
分类号:
R694.3; R969; R977.6
文献标志码:
A
摘要:

目的      探讨内质网应激在大鼠间质性膀胱炎发病过程中的作用,以及4-PBA的治疗价值。      方法      45只雌性SD大鼠按随机数字表法分为3组:对照(C)组、炎症(IC)组和炎症+4-PBA(IC+4-PBA)组,每组15只。C组用生理盐水处理;IC组用鱼精蛋白联合LPS诱导;IC+4-PBA组由炎症模型建立时予以内质网应激抑制剂4-PBA处理。5 d后应用Western blot分别测定内质网应激标记物(GRP78)、自噬流标记物(P62)、自噬标记物(LC3A/B、Beclin1)的表达量;免疫荧光检测膀胱LC3A/B的表达;HE染色检测膀胱组织病理学变化;尿动力学检测膀胱功能改变。      结果      IC组GRP78、P62、LC3A/B、Beclin1表达显著高于C组(P<0.05);4-PBA+IC组GRP78、P62、LC3A/B、Beclin1表达显著低于IC组;免疫荧光结果显示IC+4-PBA组LC3A/B表达显著低于IC组且高于C组(P<0.05);HE染色结果显示IC+4-PBA组膀胱上皮组织完整性,炎细胞浸润和组织水肿程度都较IC组明显改善;在膀胱功能学上,IC+4-PBA组大鼠较IC组排尿频率显著降低,排尿间隔显著延长。      结论      在鱼精蛋白联合LPS诱导的大鼠间质性膀胱炎模型中,使用4-PBA抑制膀胱内质网应激恢复自噬流有可能降低膀胱兴奋性,改善膀胱功能。

Abstract:

Objective      To investigate the role of endosplasmic reticulum stress (ERS) in protamine/lipopolysaccharide (PS/LPS)-induced interstitial cystitis (IC), and the potential therapeutic value of 4-phenylbutyric acid (4-PBA) in rats.       Methods      Forty-five female Sprague-Dawley rats were randomly divided into control group (C group), IC group and IC+4-PBA group, with 15 rats in each group. IC model was established with PS/LPS infusion in bladder, while saline infusion was adopted in the control rats. The rats in the IC+4-PBA group received the same bladder infusion as the rats in the IC group, and 4-PBA solution was administered intragastrically once a day. In 5 d later, ERS biomarker (GRP78), autophagy biomarkers (LC3A/B, Beclin1) and autophagy flux biomarker (P62) were assessed by Western blotting. Immunofluorescence staining of LC3A/B was conducted. The histopathologic changes of the bladder were observed by HE staining, and urination function was evaluated by urodynamic test.       Results      In the IC group, GRP78, LC3A/B, Beclin1 and P62 were increased as compared with the C group (P<0.05), and after 4-PBA was used to inhibit the ERS, these biomarkers were decreased. Immunofluorescence staining results revealed lower LC3A/B expression in the IC+4-PBA group than in the IC group and higher expression than in the C group (P<0.05). HE staining results showed that the bladder epithelial tissue integrity, inflammatory cell infiltration and tissue edema degree were improved significantly in the IC+4-PBA group. As for bladder urination function, compared with the IC group, the bladder urination frequency was decreased significantly and the urination interval was significantly prolonged in the IC+4-PBA group.       Conclusion      4-PBA down-regulates the bladder excitation and protects the bladder function by inhibiting the ERS and restoring the autophagy flux in PS/LPS-induced IC.

相似文献/References:

[1]亢胜男,刘疏柯,刘贤,等.Chromofungin调控自噬流改善脓毒症小鼠肺组织炎症损伤[J].第三军医大学学报,2021,43(14):1332.
 KANG Shengnan,LIU Shuke,LIU Xian,et al.Chromofungin regulates autophagy flux to improve lung tissue inflammation in septic mice[J].J Third Mil Med Univ,2021,43(11):1332.

更新日期/Last Update: 2016-05-29