School of Life Sciences, Shanghai University, 333 Nanchen Road, Shanghai 200444, PR China.
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, 138 Yixueyuan Road, Shanghai 200032, PR China; School of Medical Technology, Jiangsu Vocational College of Medicine, 283 South Jiefang Road, Yancheng 224005, PR China.
Auton Neurosci. 2018 Sep;213:71-80. doi: 10.1016/j.autneu.2018.06.003. Epub 2018 Jun 12.
The lack of precise therapies for stress-induced hypertension highlights the need to explore the process of blood pressure changes. Studies have shown that neuroinflammation in the central nervous system is associated with hypertension, although the mechanisms remain elusive. Microglia, are known to play dualistic protective and destructive roles, representing logical but challenging targets for improving stress-induced hypertension. Here, as a model, we used rats with stress-induced hypertension, and found that a switch from an immunoregulatory (M2) to a pro-inflammatory (M1) dominant response occurred in microglia during development of stress-induced hypertension. Administration of minocycline, which is commonly used to inhibit microglial M1 polarisation, attenuated the increase in activated microglia and M1 microglial markers expression in the hypothalamic paraventricular nucleus of rats with stress-induced hypertension. To shed further light on development of stress-induced hypertension, we examined changes in pro- and anti-inflammatory cytokines, and found increased expression of M2 microglial markers during early pathogenesis. Based on these results, we propose the possibility that M1/M2 microglia are related to development of stress-induced hypertension. Consequently, a target molecule that skews M2 polarisation of microglia may be a beneficial therapy for this disease.
应激性高血压缺乏精确的治疗方法，突出了探索血压变化过程的必要性。研究表明，中枢神经系统的神经炎症与高血压有关，但机制仍不清楚。小胶质细胞具有双重保护和破坏作用，是改善应激性高血压的合理但具有挑战性的靶点。在这里，我们使用应激性高血压大鼠作为模型，发现在应激性高血压发展过程中小胶质细胞中从免疫调节（M2）向促炎（M1）优势反应转变。米诺环素是一种常用于抑制小胶质细胞 M1 极化的药物，它可减轻应激性高血压大鼠下丘脑室旁核中活化小胶质细胞和 M1 小胶质细胞标志物表达的增加。为了进一步阐明应激性高血压的发展，我们检查了促炎和抗炎细胞因子的变化，发现在早期发病过程中 M2 小胶质细胞标志物的表达增加。基于这些结果，我们提出 M1/M2 小胶质细胞可能与应激性高血压的发展有关。因此，偏向小胶质细胞 M2 极化的靶向分子可能是治疗这种疾病的有益方法。
