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目的观察RNA干扰免疫蛋白酶体亚基低分子重量蛋白2(LMP2)对大鼠脑缺血再灌注后神经炎症反应的影响。方法线栓法制作SD大鼠大脑中动脉阻塞再灌注(MCAO)模型,脑缺血1 h再灌注72 h。SD大鼠按照体重随机分为假手术组、实验组和对照组,每组10只。实验组和对照组分别在MCAO术前1 h,立体定位脑内注射慢病毒载体LMP2-shRNA及阴性对照shRNA液体。用Western blot法分析LMP2、LMP7、磷酸化核因子-κB p65(NF-κB p65)蛋白表达,用ELISA法测定脑组织白介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)的浓度。结果局灶性脑缺血再灌注后,梗死灶周边的皮层和纹状体区LMP2、NF-κB、IL-1β和TNF-α蛋白表达上调,注射慢病毒LMP2-shRNA载体可显著下调这些蛋白产生,减少脑梗死体积,且未见明显的药物不良反应。结论RNA干扰LMP2表达,可显著下调脑缺血后神经炎症反应,发挥神经保护作用。
Objective To observe the effect of LMP2, an inhibitor of RNA interference on neuroinflammation after cerebral ischemia / reperfusion in rats. Methods The middle cerebral artery occlusion and reperfusion (MCAO) model of middle cerebral artery occlusion (SDAO) was established by thread occlusion. SD rats were randomly divided into sham operation group, experimental group and control group according to body weight, with 10 rats in each group. The experimental group and the control group were injected with lentiviral vector LMP2-shRNA and negative control shRNA liquid stereotaxis 1 h before MCAO respectively. The expressions of LMP2, LMP7 and NF-κB p65 protein were analyzed by Western blot. The levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF- concentration. Results After focal cerebral ischemia-reperfusion, the expression of LMP2, NF-κB, IL-1β and TNF-α in the cortex and striatum around the infarct area were increased. Injection of lentivirus LMP2-shRNA vector significantly down-regulated these proteins Produce, reduce the volume of cerebral infarction, and no obvious adverse drug reactions. Conclusion The RNA interference of LMP2 expression can significantly reduce the neuroinflammation reaction after cerebral ischemia and exert the neuroprotective effect.