雷帕霉素对脑缺血再灌注损伤保护效应的研究

Study on the protective effects of rapamycin on cerebral ischemia-reperfusion injury in rats

摘要:

目的：采用双侧颈总动脉阻断的方法制作全脑缺血再灌注动物模型，研究雷帕霉素（Rapamycin，Rapa）对大鼠脑缺血再灌注损伤是否有保护效应。方法：用双侧颈总动脉阻断法制作脑缺血模型，缺血前侧脑室给予Rapa，缺血20 min，再灌24 h后固定，取脑，做连续冠状冰冻切片，焦油紫染色，光镜下观察拍照，无偏差计数，比较假手术组（SO组）、治疗对照组（TC组）、Rapa治疗组（RI组）的细胞密度。结果：①与SO组比较，TC组前额皮层及颞叶皮层的分子层细胞均明显减少（P<0.05）。②与TC组比较，缺血前12 h给予Rapa组的颞叶分子层细胞明显增多（P<0.05）。③与TC组比较，缺血前30 min给予Rapa组和缺血前12 h给予Rapa组的前额分子层细胞均增多，但缺血前12 h给予Rapa组的增加更明显（P<0.05）。结论：Rapa对大鼠脑缺血再灌注损伤有保护效应，且这一保护效应和给药时间密切相关。

Abstract:

Objective：To investigate the protective effects of rapamycin on cerebral ischemia-reperfusion injury in rats，with the model of global cerebral ischemia-reperfusion established by means of ligating bilateral carotid arteries. Methods：Cerebral ischemia was produced by transient occlusion of bilateral carotid arteries for 20 minutes. The rapamycin treated group received an intracerebroven－tricular injection of rapamycin（10 mmol/L） 30 minutes and 12 hours before cerebral ischemia.Serial coronal sections of the brains were collected every 250 ?滋m 24 hours after ischemia-reperfusion，then each frozen brain slice was selected to stain using cresyl violet and observed under light microscope unbiased counting method was used to calculate the cell density of the sham-operation （SO） group，treatment control （TC） group and rapamycin injection （RI） group. Results：①The cells of prefrontal cortex and temporal lobe in the molecular layer in TC group reduced obviously compared with SO group（P<0.05）.②The cell density of the temporal lobe molecular layer in RI group 12 hours before ischemia increased significantly compared with TC group（P<0.05）.③The cell density of the pre－frontal cortex in RI group both 30 minutes and 12 hours before cerebral ischemia was higher than that in TC group and the increase in RI group 12 hours before cerebral ischemia was much more significant（P<0.05）. Conclusion：Rapamycin has protective effects a－gainst cerebral ischemia-reperfusion injury in rats，and the protective effects are closely related to the administration time.