尿氧化应激和ERK激活中等 HMGB1诱导的膀疼痛
Shaojing Ye1, Dlovan F D Mahmood1, Fei Ma1
1Lexington VA Health Care System, Research & Development, Lexington, KY 40502, USA.
Cells
|July 6, 2023
概括
高流动性组盒-1 (HMGB1) 通过增加泌尿器氧化应激和ERK激活,引起膀疼痛. 用抗氧化剂或ERK抑制剂阻断这些通路可以缓解HMGB1诱导的膀疼痛.
科学领域:
- 泌尿器科 泌尿器科 泌尿器科 泌尿器科
- 疼痛研究 疼痛研究
- 分子生物学分子生物学
背景情况:
- 蛋白酶激活受体-4 (PAR4) 激活会通过巨细胞迁移抑制因子 (MIF) 和高流动性组盒-1 (HMGB1) 引起膀疼痛.
- HMGB1在膀疼痛中的特定下游信号,独立于MIF,需要阐明.
研究的目的:
- 通过检查MIF缺陷小鼠的氧化应激和ERK激活来研究HMGB1诱导的膀疼痛机制.
- 为了确定是否针对这些途径可以缓解膀疼痛.
主要方法:
- 小鼠接受了静脉注射二硫化物HMGB1,随后使用西斑和免疫组织化学分析膀组织以检测氧化应激 (4HNE) 和ERK激活 (-ERK1/2) 的情况.
- 膀疼痛通过下腹机械值来评估.
- 在HMGB1或PAR4激活之前,小鼠接受了抗氧化剂 (NACA) 或ERK抑制剂 (FR180204) 的预治疗.
主要成果:
- HMGB1治疗增加了尿路4HNE和-ERK1/2染色,表明氧化应激增加和ERK激活.
- 用NACA或FR进行预治疗显著预防HMGB1诱导的膀疼痛.
- 没有观察到排泄参数,炎症或的显著变化.
结论:
- HMGB1通过下游尿氧化应激和ERK1/2激活来调解膀疼痛.
- 针对HMGB1的信号通路,特别是氧化应激和ERK激活,为膀疼痛提供了潜在的治疗策略.
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