Silencing miRNA-324-3p protects against cerebral ischemic injury via regulation of the GATA2/A1R axis

Previous studies have suggested that miR-324-3p is related to the pathophysiology of cerebral ischemia,but the mechanism underlying this relationship is unclea r.In this study,we found that miR-324-3p expression was decreased in patients with acute ischemic stroke and in in vitro and in vivo models of ischemic stro ke.miR-324-3p agomir potentiated ischemic brain damage in rats subjected to middle cerebral artery occlusion,as indicated by increased infarct volumes and cell apoptosis rates and greater neurological deficits.In a PC12 cell oxygen-glucose deprivation/reoxygenation model,a miR-324-3 p mimic decreased cell viability and expression of the anti-apoptotic protein BCL2 and increased expression of the pro-apoptotic protein BAX and rates of cell apoptosis,whereas treatment with a miR-324-3p inhibitor had the opposite effects.Silencing miR-324-3p increased adenosine A1 receptor(A1R)expression thro ugh regulation of GATA binding protein 2(GATA2).These findings suggest that silencing miR-324-3p reduces ischemic brain damage via the GATA2/A1R axis.

大鼠脑缺血预处理对额叶神经细胞凋亡和P^(53)蛋白表达的影响

目的 探讨大鼠短暂性全脑缺血预处理对再次脑缺血额叶神经细胞凋亡和P53蛋白表达的影响。方法 采用改良的 Pulsinelli 4血管阻断(4VO)方法,建立SD大鼠急性全脑缺血及预处理模型。雄性SD大鼠随机分为三组:预处理对照组,给予 3min全脑缺血;预处理缺血组,先给予3min全脑缺血,48h后在给予全脑缺血15min;缺血组,仅给予全脑缺血15min。采用 TUNEL方法观察额叶神经细胞凋亡,SP免疫组化方法检测P53蛋白的表达。结果 预处理对照组未见TUNEL阳性细胞,仅见个别 P53蛋白阳性细胞。预处理缺血组与缺血组相比,再灌注后48h、72h及7d额叶TUNEL阳性细胞数显著减少(P<0.01)。预处理缺 血组与缺血组相比,再灌注后48h、72h及7d额叶P53阳性细胞数显著减少(P<0.01)。结论 全脑缺血15min后额叶神经细胞 凋亡和P53蛋白表达增多。全脑缺血预处理能减少额叶缺血再灌注后神经细胞凋亡和P53蛋白的表达。