格列齐特对大鼠局灶性脑缺血再灌注损伤的保护作用及机制研究

Protective effects and mechanism of gliclazide on focal cerebral ischemia-peperfusion injuries in rats

目的：以大脑中动脉栓塞（MCAO）/再灌注模型为研究对象,探讨格列齐特对缺血性脑卒中的保护作用及机制。方法：雄性Wistar大鼠采用线栓法进行2 h左侧MCAO/再灌注,对不同再灌注时间点的梗死核心区样本检测mRNA水平及SUR1蛋白表达水平;不同剂量格列齐特静脉注射到右颈内静脉后灌注12 h,采用TUNEL法检测凋亡细胞数量、采用Bederson试验评价神经功能缺损、采用TTC染色法观察脑梗死体积。结果：SUR1 mRNA和蛋白水平在MCAO/再灌注组织中显著上调,在缺血后8~12 h达到最大水平。格列齐特可减少TUNEL阳性细胞数量,减轻神经功能损伤和脑梗死体积。结论：研究表明SUR1信号通路可能与MACO/再灌注损伤及梗死相关,静脉注射格列齐特可通过抑制SUR1的表达减轻梗死程度,减少MACO/再灌注造成的梗死面积及脑细胞凋亡程度。

OBJECTIVE To explore protective effects and mechanism of gliclazide on focal cerebral ischemia-reperfusion injuries in rat model of middle cerebral artery embolism（MCAO）/reperfusion.METHODS Male Wistar rats were treated by using2 h line switch method to induce left MCAO/reperfusion.SUR1 mRNA level and protein expression level were determined in infarct core samples at different reperfusion time points.Different doses of gliclazide were intravenously transfused into right internal jugular vein for perfusion for 12 h.TUNEL method was used to detect apoptotic cells,Bederson test to evaluate defect of nerve functions,and TTC staining method to observe cerebral infarction volume.RESULTS SUR1 mRNA and protein levels rose significantly in MCAO/reperfusion group,and ischemia reached the maximum level after 8-12 h.Gliclazide reduced number of TUNEL positive cells,and alleviated nerve function injuries and reduced cerebral infarction volume.CONCLUSIONSUR1 signaling pathway may be associated with MACO/reperfusion injuries and infarction.Intravenous administration of gliclazide can inhibit expression of SUR1,and reduce severity of infarction and infarction volume caused by MACO/reperfusion,and degree of apoptosis of brain cells.