抑制MicroRNA-27b调控Nrf2/ARE信号通路对高血压性脑出血大鼠模型脑损伤的机制研究  

Inhibiting MicroRNA-27b Regulation of Nrf2/ARE Signaling Pathway on Brain Injury in Rat Model of Hypertensive Cerebral Hemorrhage

作　　者：刘小江 李军 管义祥 LIU Xiaojiang;LI Jun;GUAN Yixiang(People's Hospital of Hai'an,Jiangsu Haian 226600,China)

机构地区：[1]江苏省海安市人民医院神经外科

出　　处：《河北医学》2020年第1期76-80,共5页Hebei Medicine

基　　金：江苏省南通市市级科技计划,(项目编号:YYZ17006);江苏省南通市市级科技计划,(项目编号:GJZ17040);江苏省第五期“333工程”科研资助项目,(项目编号:BRA2016187)

摘　　要：目的: 探讨抑制MicroRNA-27b(miR-27b)对高血压性脑出血(HICH)大鼠模型脑损伤的影响,并通过给予miR-27b拮抗剂干预,检测Nrf2/ARE信号通路及其下游蛋白的表达变化,探索miR-27b在高血压性脑出血中抗氧化和神经炎症的治疗机制。 方法: 高血压大鼠自体血脑内注入法建立高血压性脑出血大鼠模型。qRT-PCR检测高血压性脑出血大鼠出血部位脑组织miR-27b和Nrf2 mRNA表达;Western Blot实验检测miR-27b拮抗剂给药前后Nrf2/ARE信号通路蛋白核因子相关因子2(Nrf2)、血红素加氧酶(HO-1)、醌氧化还原酶(Nqo1)表达变化;试剂盒检测高血压性脑出血大鼠给药前后超氧化物歧化酶(SOD)、肿瘤坏死因子α(TNF-α)和白细胞介素1β(IL-1β)变化;TUNEL法和流式细胞分析法检测高血压性脑出血大鼠给药前后神经细胞凋亡情况。 结果: miR-27b水平受HICH影响呈现出先降低后升高的变化趋势,Nrf2 mRNA水平则呈现出先升高后降低的变化,miR-27b和Nrf2 mRNA水平前后变化具有统计学差异(P<0.05);miR-27b拮抗剂可诱导Nrf2/ARE通路Nrf2、HO-1、Nqo1蛋白表达上升;注射miR-27b拮抗剂可缓解HICH大鼠的氧化应激反应(OS)以及降低炎症因子TNF-α和IL-1β表达;miR-27b拮抗剂具有缓解HICH大鼠神经细胞凋亡、降低脑损伤的作用。 结论: 抑制miR-27b表达可明显减轻大鼠高血压性脑出血脑损伤程度,其机制可能与抗氧化信号通路Nrf2/ARE激活有关。Objective: To investigate the effect of microrna-27b (mir-27b) inhibition on brain injury in hypertensive cerebral hemorrhage (HICH) rats, and to detect the expression of Nrf2 / are signal pathway and its downstream protein through the intervention of mir-27b antagonist, and to explore the therapeutic mechanism of mir-27b in anti-oxidation and neuroinflammation in hypertensive cerebral hemorrhage. Methods: The model of hypertensive intracerebral hemorrhage was established by injecting blood into the brain. QRT-PCR was used to detect the expression of mir-27b and Nrf2 mRNA in the brain of rats with hypertensive intracerebral hemorrhage;Western blot was used to detect the expression of Nrf2 / are signal pathway protein nuclear factor-related factor-2 (Nrf2), heme oxygenase (HO-1) and quinone oxidoreductase (NQO1) before and after administration of mir-27b antagonist;the kit was used to detect the superoxide dismutation of rats with hypertensive intracerebral hemorrhage before and after administration The changes of SOD, TNF - α and IL-1 β in rats with hypertensive cerebral hemorrhage were detected by TUNEL and flow cytometry. Results: Mir-27b and Nrf2 mRNA levels were significantly different before and after hich (P < 0.05);mir-27b antagonists could induce Nrf2, HO-1 and NQO1 protein expression in Nrf2 / are pathway;mir-27b antagonists could alleviate oxidative stress response (OS) in hich rats The mir-27b antagonist can alleviate the apoptosis of nerve cells and reduce the brain injury. Conclusion: Inhibition of mir-27b expression can significantly reduce the degree of brain injury in rats with hypertensive intracerebral hemorrhage, and its mechanism may be related to the activation of Nrf2 / are.

关 键 词：高血压脑出血 MicroRNA-27b Nrf2/ARE 脑损伤 

分 类 号：R743.34[医药卫生—神经病学与精神病学]