de Barros João Luís Vieira Monteiro, Cardoso Maíra Glória, Machado Caroline Amaral, Vieira Érica Leandro Marciano, Faleiro Rodrigo Moreira, Pedroso Vinícius Sousa Pietra, Simões E Silva Ana Cristina, de Souza Leonardo Cruz, Teixeira Antônio Lúcio, de Miranda Aline Silva
Laboratório Interdisciplinar de Investigação Médica (LIIM), Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), Av. Professor Alfredo Balena, 190, sala 281, Belo Horizonte, Minas Gerais, 30130-100, Brazil.
Laboratório de Neurobiologia, Departamento de Morfologia, Instituto de Ciências Biológicas Bloco O3, sala 245, UFMG, Av. Antônio Carlos 6627, Pampulha, Belo Horizonte, Minas Gerais, 31270-910, Brazil.
Neurol Sci. 2022 May;43(5):3353-3359. doi: 10.1007/s10072-021-05856-1. Epub 2022 Jan 4.
Traumatic brain injury (TBI) is a serious public health problem, affecting 69 million people worldwide annually. Mild TBI (mTBI) comprises the majority of the cases and remains the most neglected TBI severity. Its intricate pathophysiology involves complex cellular and molecular processes that remain uncomprehended. Although the renin-angiotensin system (RAS) has its well-known roles in blood pressure regulation and fluid balance, accumulating evidence demonstrates its active expression and signaling in the central nervous system. Over the past years, pre-clinical studies have been supporting the role of RAS in mTBI. However, particularly for human TBI, evidence is still missing. Herein, we investigated peripheral levels of angiotensin II (Ang II) and angiotensin-converting enzyme (ACE), components of RAS classical axis, as well as angiotensin-(1-7) [Ang-(1-7)] and ACE2, components of RAS counter-regulatory axis, in 28 mTBI patients and 24 healthy controls. In the first 24 h, mTBI patients displayed lower ACE (p = 0.0004) and ACE2 (p = 0.0047) concentrations and an increase in Ang II (p = 0.0234) and Ang-(1-7) (p = 0.0225) levels compared to controls. Interestingly, at 30 days follow-up, mTBI patients increased the levels of ACE (p = 0.0415) and ACE2 (p = 0.0416) along with a decrease in Ang II (p = 0.0039) and Ang-(1-7) (p = 0.0015) concentrations compared with their measures at 24 h after TBI. Also, our receiver operating curve (ROC) analysis demonstrated that ACE concentration was a good predictor of mTBI diagnosis (AUC = 0.798, p < 0.0001). The current study provides the first clinical evidence of RAS molecule's involvement in mTBI and their possible role as discriminating biomarkers.
创伤性脑损伤（TBI）是一个严重的公共卫生问题，每年影响全球6900万人。轻度创伤性脑损伤（mTBI）占大多数病例，仍然是最被忽视的TBI严重程度类型。其复杂的病理生理学涉及复杂的细胞和分子过程，目前仍未完全了解。尽管肾素-血管紧张素系统（RAS）在血压调节和体液平衡中具有众所周知的作用，但越来越多的证据表明其在中枢神经系统中也有活跃的表达和信号传导。在过去几年中，临床前研究一直支持RAS在mTBI中的作用。然而，特别是对于人类TBI，相关证据仍然缺失。在此，我们调查了28例mTBI患者和24例健康对照者外周血中血管紧张素II（Ang II）和血管紧张素转换酶（ACE）（RAS经典轴的组成部分）以及血管紧张素-（1-7）[Ang-（1-7）]和ACE2（RAS反调节轴的组成部分）的水平。在伤后的最初24小时内，与对照组相比，mTBI患者的ACE（p = 0.0004）和ACE2（p = 0.0047）浓度较低，而Ang II（p = 0.0234）和Ang-（1-7）（p = 0.0225）水平升高。有趣的是，在30天随访时，与TBI后24小时的测量值相比，mTBI患者的ACE（p = 0.0415）和ACE2（p = 0.0416）水平升高，而Ang II（p = 0.0039）和Ang-（1-7）（p = 0.0015）浓度降低。此外，我们的受试者工作特征曲线（ROC）分析表明，ACE浓度是mTBI诊断的良好预测指标（AUC = 0.798，p < 0.0001）。本研究首次提供了RAS分子参与mTBI的临床证据及其作为鉴别生物标志物的可能作用。
