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右旋美托咪啶后处理对大鼠局灶性脑缺血再灌注损伤的保护作用
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DOI:
作者:
蔡叶 严佳 吕翔 徐辉
CaiYe,YanJia,LvXiang,XU Hui.
作者单位:
上海市第九人民医院麻醉科
Department of Anesthesiology, Shanghai Ninth People’s Hospital,Shanghai jiaotong University School of Medicine。Shanghai 2000 11,China
关键词:
脑缺血再灌注;核转录因子;神经保护;右旋美托咪啶;后处理
Cerebral ischemia/reperfusion; NF-κB; Neuroprotection; Dexmedetomidine; Postconditioning.
摘要:
【摘要】 目的 研究右旋美托咪啶对大鼠脑缺血再灌注损伤的神经保护作用,探讨其可能的脑保护机制。方法 线栓法制作SD大鼠大脑中动脉缺血再灌注损伤模型。60只雄性SD大鼠200-300g随机分为4组(每组15只):Ctrl组为假手术组,Mod组为脑缺血再灌注组, Dex2为右旋美托咪啶5ug•kg-1•h-1后处理组,Pdtc组为NF-κB抑制剂组。缺血再灌注24h后,每组随机取6只进行神经功能缺损评分(Longa法)和TTC染色测量大鼠脑梗塞面积并计算百分比,另外6只TUNEL染色法检测海马CA1区细胞凋亡情况,余下3只Western-Blot检测大脑海马区域细胞核内NF-κB的活化表达情况。结果 1、 Ctrl组无神经功能缺损,神经功能评分(neurologic deficit score ,NDS)为0,TTC染色亦未见脑组织梗死。Mod组、Dex2组和Pdtc组均有明显的神经功能缺损,TTC染色亦可见明显的脑组织梗死灶;但Mod组、Dex2组和Pdtc组之间NDS差异没有统计学意义(p>0.05)。2、与Ctrl组相比,Mod组、Dex2组、Pdtc组海马CA1区细胞凋亡指数增高,其中,Dex2组、Pdtc组海马CA1区细胞凋亡比Mod组减少,差异有统计学意义(P<0.05),而Dex2组与Pdtc组差异没有统计学意义。 3、Mod组、Dex2组、Pdtc组海马区细胞核内NF-κB (p65)活化表达水平均显著升高,但与Mod组相比,Dex2组和Pdtc组NF-κB活化表达水平相对减少(P<0.05),Dex2与Pdtc组差异没有统计学意义。结论:右旋美托咪啶5 ug•kg-1•h-1后处理能够明显减少SD大鼠脑梗死面积比例和海马CA1区细胞凋亡指数。部分抑制脑缺血再灌注引起NF-κB的活化表达增加可能是右旋美托咪啶的脑保护机制之一。
To investigate the protective effect and mechanism of dexmedetomidine on the brain against incomplete ischemia reperfusion injury in the rats .Methods Fifty four male SD rats weighing 200-300g were randomly divided into 4 equal groups: Ctrl group(Ctrl), ischemia reperfusion model group(Mod), ischemia-reperfusion group treated by 5 ug•kg-1•h-1 dexmedetomidine(Dex2),ischemia-reperfusion group treated by PCTC 200mg/kg(Pdtc), The middle cerebral artery occlusion(MCAO)models were established with the method of intraluminal suture occlusion. After ischemia reperfusion for 24h, the neurologic deficit score(NDS)was evaluated. The area of cerebral infarction was observed by the TIC stain. The apoptotic index of the hippocampal CA1 region and the expression of NF-kb in hippocampal region was detected by TUNEL staining and western blot . Results There were no neurologic deficits in rats of the Ctrl group、Mod group、Dex2 group and Pdtc group, while there were significant cerebral infarction in rats of the Mod group 、Dex2 group and Pdtc group. Compared to Mod group, the cerebral infarction area were significantly decreased in Dex2 group and Pdtc group. The apoptotic index of Dex2 group and Pdtc group was significantly less than that of Mod group(p<0.O5). Compared to the Ctrl group, the positive expression of NF-κB were significantly increased in Mod group 、Dex2 group and Pdtc group. The positive expression of NF-κB were significantly lower in Dex2 group and in Pdtc group than in Mod group (p<0.O5).
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