Xu Wenzhe, Li Feng, Liu Zhiguo, Xu Zhenkuan, Sun Bin, Cao Jingwei, Liu Yuguang
Department of Neurosurgery, Qilu Hospital and Brain Science Research Institute of Shandong University, Jinan 250012, P.R. China.
Department of Neurosurgery, People's Hospital of Zhangqiu, Jinan 250200, P.R. China.
Oncotarget. 2017 Aug 7;8(41):70669-70684. doi: 10.18632/oncotarget.19974. eCollection 2017 Sep 19.
Oxidative stress and neuroinflammation are the key factors leading to secondary brain injury after intracerebral hemorrhage (ICH). We investigated the effects of miR-27b, an oxidative stress-responsive microRNA, on ICH-induced brain injury in rats. The ICH model was induced by intracerebral injection of collagenase. Following ICH, miR-27b expression in the striatum was reduced, whereas expression of Nrf2 mRNA and protein was increased. In PC12 cells, overexpression of miR-27b reduced expression of Nrf2, Hmox1, Sod1 and Nqo1, while miR-27b inhibition had the opposite effects. Dual luciferase reporter assays showed that Nrf2 mRNA was a direct target of miR-27b. Intracerebroventricular injection of miR-27b antagomir and transfection of miR-27b inhibitor inhibited endogenous miR-27b in rats and PC12 cells, respectively. MiR-27b antagomir promoted activation of the ICH-induced Nrf2/ARE pathway and reduced the lipid peroxidation, neuroinflammation, cell death and neurological deficits otherwise seen after ICH. In PC12 cells, the miR-27b inhibitor diminished iron-induced oxidative stress, inflammation and apoptosis, and those effects were blocked by Nrf2 knockdown. These results demonstrate that miR-27b inhibition alleviates ICH-induced brain injury, which may be explained in part by its regulation on the Nrf2/ARE pathway.
氧化应激和神经炎症是脑出血（ICH）后导致继发性脑损伤的关键因素。我们研究了氧化应激反应性微小RNA miR-27b对大鼠ICH诱导的脑损伤的影响。通过脑内注射胶原酶诱导建立ICH模型。ICH后，纹状体中miR-27b的表达降低，而Nrf2 mRNA和蛋白的表达增加。在PC12细胞中，miR-27b的过表达降低了Nrf2、Hmox1、Sod1和Nqo1的表达，而抑制miR-27b则产生相反的效果。双荧光素酶报告基因检测表明Nrf2 mRNA是miR-27b的直接靶点。脑室内注射miR-27b拮抗剂和转染miR-27b抑制剂分别抑制了大鼠和PC12细胞中的内源性miR-27b。miR-27b拮抗剂促进了ICH诱导的Nrf2/ARE途径的激活，并减少了ICH后出现的脂质过氧化、神经炎症、细胞死亡和神经功能缺损。在PC12细胞中，miR-27b抑制剂减轻了铁诱导的氧化应激、炎症和凋亡，而这些作用被Nrf2基因敲低所阻断。这些结果表明，抑制miR-27b可减轻ICH诱导的脑损伤，这可能部分是由于其对Nrf2/ARE途径的调控作用。
