miR-17-5p调控PTEN对大脑中动脉闭塞大鼠的神经保护作用被引量：2

Neuroprotective effects of miR-17-5p on middle cerebral artery occlusion rats by regulating PTEN

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摘要目的本文建立大脑中动脉闭塞(MCAO)模型大鼠,研究miR-17-5p(microRNA-17-5p)对模型大鼠的神经保护作用及其可能机制。方法大鼠随机分为5组:假手术组(Sham组)、模型组(MCAO组)、MCAO+mimic组、MCAO+inhibitor组和MCAO+BPV组。采用线栓法建立MCAO大鼠模型。建模24 h后,检测大鼠脑含水量和神经功能;HE染色观察大鼠脑组织病理学改变;TUNEL染色检测大鼠脑组织神经元细胞凋亡情况;预测miR-17-5p和PTEN是否存在连续的结合位点,RT-PCR检测两者mRNA表达水平;Western blot检测脑组织中PTEN、AKT和哺乳动物雷帕霉素靶点(mTOR)的磷酸化水平。结果miR-17-5p和PTEN存在连续结合位点。与模型组比较,MCAO+mimic组和MCAO+BPV组大鼠神经功能评分、脑含水量、神经细胞凋亡率、PTEN的m RNA和蛋白表达水平均显著降低(P<0.01),脑组织病理学损伤也明显改善,而miR-17-5p、p-AKT/AKT和p-mTOR/mTOR表达水平显著增加(P<0.01)。此外,MCAO+inhibitor组上述指标则正好相反(P<0.05或P<0.01)。结论miR-17-5p表达上调对MCAO大鼠具有神经保护作用,其功能发挥可能与介导调控PTEN信号通路相关。 Objective To establish a rat model of middle cerebral artery occlusion(MCAO),and to study the neuroprotective effect of microRNA-17-5 p(miR-17-5 p)on the model rats and its possible mechanism.Methods Rats were randomly divided into five groups:sham operation group(Sham group),model group(MCAO group),MCAO+mimic group,MCAO+inhibitor group and MCAO+BPV group.Thread embolism method was used to establish MCAO rat model.After 24 hours of modeling,brain water content and neurological function were measured;HE staining was used to observe the pathological changes of rat brain;TUNEL staining was used to detect neuronal apoptosis in brain tissue of rats.Predicting the existence of continuous binding sites of miR-17-5 p and PTEN,RT-PCR was used to detect the expression level of miR-17-5 p and PTEN;Western blot was used to detect the phosphorylation level of PTEN,AKT and mammalian rapamycin targets in brain tissue.Results There are continuous binding sites between miR-17-5 p and PTEN.Compared with the model group,the neurological function score,brain water content,neuronal apoptosis rate,PTEN gene and protein expression levels were significantly decreased in MCAO+mimic group and MCAO+BPV group(P<0.01),and the brain histopathological damage was also significantly improved,while the expression levels of miR-17-5 p,p-AKT/AKT and p-mTOR/mTOR were significantly increased(P<0.01);In addition,the above indicators in MCAO+inhibitor group were just the opposite(P<0.05 or P<0.01).Conclusion The up-regulation of the expression of miR-17-5 p has neuroprotective effect on MCAO rats,and its function may be related to the regulation of PTEN signaling pathway.

作者徐婉茹范倩韩凌宗碧云 XU Wan⁃ru;FAN Qian;HAN Ling;ZONG Bi⁃yun(Department of Neurology,Heze Municipal Hospital,Heze,Shandong Province 274000,China)

机构地区菏泽市立医院神经内科

出处《解剖学研究》 CAS 2020年第2期130-135,共6页 Anatomy Research

基金山东省菏泽市科学技术研究与发展计划项目(2017第07号)

关键词大脑中动脉闭塞 miR-17-5p PTEN信号通路哺乳动物雷帕霉素靶点 Middle cerebral artery occlusion miR-17-5p PTEN signaling pathway Mammalian target of rapamycin

分类号 R743 [医药卫生—神经病学与精神病学]

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