雷帕霉素对大鼠脑缺血再灌注损伤后Cathepsin D、p-Akt表达的研究-神经病学专业论文.docxVIP

万方数据 万方数据 Cathepsin D 蛋白表达 6 小时开始上升，24h 达到高峰，48h 仍保存高水平，与 模型组比较，雷帕霉素干预组 Cathepsin D 蛋白表达在各时间点均明显减弱 （p0.05）。 五、正常组及 Sham 组顶叶皮层可见少量 p-Akt 蛋白的表达；I/R 组 3h 缺血 侧 p-Akt 蛋白的表达达高峰，随时间延长逐渐降低，与正常组及假手术组相比差 异有统计学意义（P0.05）；Rap 干预后，缺血再灌注后 3 小时 p-Akt 蛋白表达 与 I/R 组 3h 组相比，蛋白表达差异无统计学意义（P0.05），6 小时明显上升， 12 小时达峰，48 小时有较高表达，差异有显著性(P0. 05 ) 。 结论： Rap 可能通过下调 Cathepsin D 蛋白、上调 p-Akt 蛋白，减轻大鼠缺血再灌 注损伤后大脑中动脉梗塞的面积及神经细胞凋亡，发挥其脑保护作用。 关键词:雷帕霉素；脑缺血再灌注损伤；细胞凋亡；神经保护药；溶酶体组织 蛋白酶 D；丝氨酸苏氨酸激酶 4 Effects of Rapamycin on expression of Cathepsin D、p-Akt after Focal Cerebral Ischeme/Reperfusion Injury in Rat ABSTRACT Objective: To investigate the changes of Lysosome Cathepsin D、p-Akt after Focal Cerebral Ischeme/Reperfusion injury in rat, and the protective effect of rapamycin on the cerebral ischemic injury in animals. Methods: 100 healthy male Sprague-Dawley(SD) rats which weight 280±20g and 10~12weeks old were randomly divided into four groups: normal group(n=10); sham-operated group(n=30); injury reperfusion injury(I/R) group(n=30); Rap group(n=30).The middle cerebral artery ischemia and reperfusion model in rats was achieved by an intraluminal filament embolism for 2 hours.The rapamycin treated group received an intracerebroventricular injection of rapamycin 5μL（10 mmol/L） before ischemia 30 minutes.The rats of model group and I/R group were immediately injected withthe same volume DMSO. The neurological deficit scores were evaluated with long’s five-point scale stardard scoring method. Using TTC dyeing to detect cerebral infarction volume change,The neuronal apoptosis was detected by the method of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL). The expression of cathepsin D and p-Akt protein were measured with methods of immunohistochemistry respectively at 3h, 6h, 12h, 24h and 48h after reperfusion in cerebral cortex of rats. Results: Middle cerebral artery occlusion models were achived in 72.29%. Compared with I/R group, the group of rapamycin can decrease n