柏柏林通过通过高血压的肠道微生物群对TMAO-内质网膜应激通路进行下调来改善血管功能障碍
Zhichao Wang1, Yijia Shao2, Fang Wu2
1The International Medical Department, Shenzhen Hospital, Southern Medical University, Shenzhen, China; Integrative Microecology Clinical Center, Shenzhen Key Laboratory of Gastrointestinal Microbiota and Disease, Shenzhen Hospital, Southern Medical University, Shenzhen, China.
Microbiological research
|July 25, 2024
概括
柏柏林 (BBR) 通过抑制肠道细菌,改善血管功能和降低高血压的血压来降低三甲基胺N氧化物 (TMAO). 这项研究揭示了BBR.
科学领域:
- 心血管研究研究心血管研究
- 微生物组科学 微生物组科学
- 药理学 药理学是指药理学的学科.
背景情况:
- 三甲基胺N氧化物 (TMAO) 是一种肠道微生物代谢物,与高血压和血管功能障碍有关.
- 柏柏林 (BBR) 已知对心血管有好处,可能通过调节肠道微生物群-代谢物通路.
- 在高血压中,BBR影响TMAO诱导的血管问题的具体机制尚未完全理解.
研究的目的:
- 调查TMAO在高血压相关的血管功能障碍中的作用.
- 确定柏柏林 (BBR) 是否以及如何缓解高血压中TMAO诱导的血管功能障碍.
- 探索BBR对TMAO生产和肠道微生物群组成的影响.
主要方法:
- 对高血压患者和对照患者的血TMAO水平和肠道细菌丰度的分析.
- 在体外研究TMAO对内皮细胞和内质网膜应激 (ERS) 的作用.
- 在体内研究中,使用了用BBR治疗的胆-血管新生素II高血压小鼠模型.
- 用BBR治疗的高血压患者的临床研究评估TMAO水平,血管功能和血压.
- 便16S rDNA测序以分析肠道微生物群的变化.
- 在体外细菌培养和酶抑制试验中,研究BBR对TMAO生物合成的影响.
主要成果:
- 在高血压患者中,高血TMAO和特定细菌丰度与血管功能受损相关.
- 在体外,TMAO激活了内质网膜应激 (ERS) 信号,导致内皮细胞功能障碍和亡.
- 在小鼠和高血压患者中,BBR治疗显著降低了血TMAO水平,并改善了血管功能.
- 在小鼠模型和高血压患者中,BBR的使用降低了血压.
- BBR改变了肠道细菌的组成,特别是减少了参与TMAO生物合成的CutC/D细菌的丰富性.
- BBR直接抑制了CutC/D酶,减少了肠道微生物群的TMAO前体的产生.
结论:
- 在高血压中,TMAO有助于血管功能障碍,部分是通过内质网膜应激.
- 柏柏林通过抑制肠道微生物CutC/D酶,有效降低TMAO水平,从而改善血管功能,降低高血压的血压.
- 通过准肠道微生物群-TMAO轴,BBR代表了高血压的潜在治疗策略.
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