Miranda Aline Silva, Rachid Milene Alvarenga, Souza Cássio Ferraz, Oliveira Bruna da Silva, Ferreira Rodrigo Novaes, Martinelli Patrícia Massara, Teixeira Antônio Lúcio, Camargos Elizabeth R S, Simões E Silva Ana Cristina
Laboratório de Neurobiologia, Departamento de Morfologia, Instituto de Ciências Biológicas, UFMG, Belo Horizonte, Minas Gerais, Brazil; Laboratório Interdisciplinar de Investigação Médica, Faculdade de Medicina, UFMG, Belo Horizonte, Minas Gerais, Brazil.
Departamento de Patologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil.
Acta Trop. 2019 Jun;194:36-40. doi: 10.1016/j.actatropica.2019.03.020. Epub 2019 Mar 18.
Chagas' disease (CD) is a zoonosis caused by the protozoan Trypanosoma cruzi. Besides being an important cause of cardiomyopathy, central nervous system (CNS) manifestations have also been reported in CD. Renin-Angiotensin System (RAS) plays a pathophysiological role in several brain disorders such as cerebrovascular and neurodegenerative diseases. A link between RAS and nitric oxide (NO) pathways has been described in CNS. For instance, Angiotensin-(1-7) increases NO expression in the brain, which may, in turn, help to control parasite load in response to T. cruzi infection. Herein, we investigated the levels of RAS components in the brain cortex in acute T. cruzi infection and the effect of L-NAME administration, an inhibitor of the enzyme NO synthase, in CNS infection and in RAS molecules. Male Holtzman rats were inoculated intraperitoneally with T. cruzi Y strain and received L-NAME or tap water from one day before the infection until 13 days post infection (dpi). Parasitemia was evaluated on alternate days from day 3 post-infection until day 13 in both T. cruzi infected groups. Histopathological analysis of the brain cortex was also performed. Brain cortex was collected from non-infected (controls) and infected rats at 13 dpi for RAS components assessment. Infected rats receiving L-NAME presented higher parasitemia, brain parasitism and inflammation compared with non-treated infected animals. The administration of L-NAME significantly decreased the levels of Angiotensin I Converting Enzyme 2 (ACE2). In conclusion, we provided preliminary evidence of the interaction between RAS and NO during the acute phase of T. cruzi infection.
恰加斯病（CD）是由原生动物克氏锥虫引起的一种人畜共患病。除了是心肌病的重要病因外，CD患者也有中枢神经系统（CNS）表现的报道。肾素-血管紧张素系统（RAS）在几种脑部疾病如脑血管疾病和神经退行性疾病中发挥病理生理作用。中枢神经系统中已描述了RAS与一氧化氮（NO）途径之间的联系。例如，血管紧张素-（1-7）可增加大脑中NO的表达，这反过来可能有助于控制对克氏锥虫感染的寄生虫负荷。在此，我们研究了急性克氏锥虫感染时大脑皮质中RAS成分的水平，以及给予L-NAME（一种一氧化氮合酶抑制剂）对中枢神经系统感染和RAS分子的影响。雄性霍尔兹曼大鼠腹腔接种克氏锥虫Y株，并从感染前一天至感染后13天（dpi）接受L-NAME或自来水。在两个克氏锥虫感染组中，从感染后第3天到第13天隔天评估寄生虫血症。还对大脑皮质进行了组织病理学分析。在13 dpi时从未感染（对照）和感染大鼠中收集大脑皮质用于评估RAS成分。与未治疗的感染动物相比，接受L-NAME的感染大鼠表现出更高的寄生虫血症、脑寄生虫感染和炎症。给予L-NAME显著降低了血管紧张素I转换酶2（ACE2）的水平。总之，我们提供了克氏锥虫感染急性期RAS与NO之间相互作用的初步证据。
