目的 探讨表观遗传学信号分子BET蛋白的抑制剂JQ1对脑缺血再灌注损伤的保护作用和机制.方法 选择成年雄性Wistar大鼠55只,并随机分为对照组、模型组和实验组,利用线栓法制造大鼠脑缺血再灌注损伤模型.实验组在造模的同时给予JQ1干预.24 h后处死所有实验动物,并通过Zea-Longa神经行为学评分、TTC染色、HE染色、ELISA法等方法,检测大鼠的神经功能、脑梗死体积、脑组织病理学改变、变性细胞指数(DCI)以及脑组织炎症因子[肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)和白细胞介素-6(IL-6)]的水平.结果 模型组和实验组大鼠的神经行为学评分较对照组均明显增高(P<0.05),但实验组大鼠的神经行为学评分较模型组明显下降(P<0.05);模型组大鼠的脑梗死体积、DCI明显高于对照组(P<0.05);当给予JQ1干预后,虽然实验组大鼠脑梗死体积、DCI仍然高于对照组(P<0.05),但是较模型组已明显下降(P<0.05);模型组大鼠脑组织的炎症因子IL-6、IL-1β、TNF-α的水平明显高于对照组(P<0.05);当给予JQ1干预后,虽然实验组大鼠脑组织的炎症因子IL-6、IL-1β、TNF-α的水平仍然高于对照组(P<0.05),但较模型组已明显下降(P<0.05).结论 BET蛋白的抑制剂JQ1对大鼠脑缺血再灌注损伤具有保护作用,其机制可能与JQ1具有抑制炎症因子表达的作用有关.%Objective To investigate the protective effect of BET protein inhibitor JQ 1 on cerebral ischemia reperfusion injury.Methods Totally 55 male Wistar rats were divided into control group, model group and treatment group.The cerebral ischemia -reperfusion rats were established by inserting a monofilament into middle cerebral artery. And the rats in the treatment group were administered with JQ 1.All rats were executed at the 24th hour.The neurological function scores were observed.The infarct size was measured by TTC staining.The morphological change of nerve cell and the denatured cell index(DCI)were observed by HE staining.The expressions of IL-6,IL-1βand TNF-αwas deter-mined by ELISA.Results The neurological function scores in model group and treatment group were significantly in -creased compared with those in control group(P<0.05).The neurological function scores in treatment group were signif-icantly reduced compared with those in model group(P<0.05).The infarct size and DCI in the model group were signifi-cantly increased compared with those in control group(P<0.05),which were mitigated by JQ1.The expression of IL-6,IL-1βand TNF-αin model group was significantly increased compared with those in the control group(P<0.05), which was reduced by JQ1.Conclusion The protective effect of JQ1 on cerebral ischemia reperfusion injury in rats is correlated with its inhibition of inflammatory response.
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