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β-腺素受体调节尿路炎症,并在膀出口阻塞模型中阻塞区域

Xiaoshuai Gao¹, Xi Jin¹, Wei Wang¹

¹Department of Urology and Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, Chengdu, Sichuan, PR China.

International immunopharmacology

|December 16, 2023

概括

贝塔腺素受体 (ADRB) 激动剂通过增加区域封闭体 (ZO) 表达和减少炎症来改善尿路屏障功能,在老鼠膀出口阻塞模型和体外实验室中. 这些效应通过RhoA/ROCK通路进行介导.

科学领域:

泌尿器科泌尿器科泌尿器科泌尿器科
细胞生物学细胞生物学
药理学药理学是指药理学的学科.

背景情况:

膀出口阻塞 (BOO) 诱导尿道炎症并破坏上皮屏障.
β-腺受体 (ADRBs) 在调节泌尿器功能方面发挥作用.
Zonula occludens (ZO) 蛋白质对于保持尿路膜屏障完整性至关重要.

研究的目的:

在大鼠PBOO模型中研究ADRBs对尿路炎症和ZO表达的影响.
为了评估ADRB激动剂在体外泌尿道细胞模型中的作用.

主要方法:

建立了一种大鼠部分膀输出阻塞 (PBOO) 模型.
大鼠接受了ADRB2或ADRB3激动剂的治疗.
人类尿细胞 (HUCs) 在体外模型中使用激素治疗或水静压.
评估了炎症性细胞因子 (MCP-1,IL-6,RANTES) 和ZO蛋白 (ZO-1,ZO-2) 的表达.
研究了RhoA/ROCK信号通路的参与.

主要成果:

PBOO显著增加了炎症性细胞因子,并降低了ZO-1/ZO-2表达.
ADRB2和ADRB3激动剂降低了炎症性细胞因子的调节,并在体内和体外增加了ZO的表达.
罗亚和ROCK抑制剂减少了水静压诱导的炎症.
罗亚激动剂逆转了ADRB激动剂的抗炎作用.

结论:

ADRB2和ADRB3激动剂通过增加ZO蛋白表达来增强尿屏障功能.
通过调节RhoA/ROCK信号通路,ADRB激动剂可以抑制尿炎.
向ADRB可能为BOO诱导的泌尿器功能障碍提供治疗策略.

关键词:

膀出口的阻塞膀出口的阻塞人类泌尿细胞炎症炎症是一种炎症.佐努拉 (Zonula) 被封闭了.这是β-腺素受体.

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