ACE2/Ang-(1-7)/Mas受体轴抗炎作用：基础和临床研究的证据
2018/01/05
摘要
背景：RAS系统在炎症和纤维化过程中发挥重要作用。经典RAS轴由ACE,Ang-II和AT1组成，通过激活不同细胞功能和分子信号通路从而造成组织损伤，炎症和纤维化发生。与之相对，由ACE2,Ang-(1-7)和Mas受体组成的RAS轴则发挥与经典轴相反的作用。
目的：本篇综述旨在小结当前ACE2/Ang-(1-7)/Mas受体轴抗炎和抗纤维化相关基础研究，人体疾病和临床研究。结果：多项研究提示ACE2/Ang-(1-7)/Mas受体轴可以减少细胞因子释放并抑制纤维化信号通路，包括粥样硬化、脑缺血、肥胖、慢性肾病、肝病和哮喘。另一方面，临床研究数据较少。
结论：实验研究明确指出ACE2/Ang-(1-7)/Mas受体轴抗炎和抗纤维化作用。临床研究，尤其是III期和IV期研究有助于更好评价ACE2/Ang-(1-7)/Mas受体轴治疗不同疾病炎症的作用。
（上海交通大学医学院附属瑞金医院呼吸与危重症医学科 周剑平 万欢英 摘译）
（Curr Drug Targets. 2017;18(11):1301-1313. doi: .2174/1389450117666160727142401.）
（Curr Drug Targets. 2017;18(11):1301-1313. doi: .2174/1389450117666160727142401.）
The Anti-Inflammatory Potential of ACE2/Angiotensin-(1-7)/Mas Receptor Axis: Evidence from Basic and Clinical Research.
Curr Drug Targets. 2017;18(11):1301-1313. doi: .2174/1389450117666160727142401.
Rodrigues Prestes TR, Rocha NP, Miranda AS, Teixeira AL, Simoes-E-Silva AC.
Abstract
BACKGROUND:The renin angiotensin system (RAS) plays an important role in inflammation and fibrosis. The classical axis of the RAS, formed by angiotensin converting enzyme (ACE), angiotensin II (Ang II) and angiotensin receptor type 1 (AT1), activates several cell functions and molecular signaling pathways related to tissue injury, inflammation and fibrosis. In sharp contrast, the RAS axis composed by angiotensin converting enzyme 2 (ACE2), angiotensin-(1-7) and Mas receptor exerts opposite effects in relation to inflammatory response and tissue fibrosis.
OBJECTIVE:In this review, we have the aim to summarize recent findings on the anti-inflammatory and anti-fibrogenic role of ACE2/Ang-(1-7)/Mas axis in the context of basic research, experimental human dis-eases and clinical studies.
RESULTS:Several studies showed that ACE2/Angiotensin-(1-7)/Mas axis reduces cytokine release and inhibits signaling pathways of tissue fibrosis in experimental models of human diseases including atherosclerosis, cerebral ischemia, obesity, chronic kidney disease, liver diseases and asthma. On the other hand, very few data was provided by clinical studies.
CONCLUSION:Experimental studies clearly support the anti-inflammatory and anti-fibrotic effects of ACE2/ Ang-(1-7)/Mas axis. Clinical studies, especially phase III and IV trials, will be necessary to establish the therapeutic role of ACE2/Ang-(1-7)/Mas axis in controlling inflammation in different human diseases.
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β2-肾上腺素能受体激动剂对重度哮喘患者纤维细胞功能的抑制作用降低
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Ang-(1-7)/Mas受体敲除小鼠慢性过敏性肺部炎症显著加重
