Objective: To investigate whether rapamycin treatment starting at 24 h after cerebral ischemia/reperfusion(I/R) has protective effect on brain injury in rats.
Methods: The rat I/R model was established by middle cerebral artery occlusion according to Longa's method. A total of 104 Sprague Dawley rats were randomly divided into sham group, model group, and rapamycin-treated groups (6 h or 24 h after modeling). Neurological function was assessed with neurological severity score (NSS). Triphenyl tetrazolium chloride (TTC) staining and Fluoro-Jade B (FJB) staining were used to examine the infarct volume and neuronal apoptosis, respectively. The expression of p-S6 protein in mTOR signaling pathway was detected by Western blot analysis.
Results: Compared with sham group, NSS of the model group was significantly increased and TTC staining indicated obvious infarct area (all P<0.01). Furthermore, significantly increased number of FJB-positive cells and p-S6 expression in the penumbra area were shown in the model group (all P<0.01). Compared with the model group, both rapamycin-treated groups demonstrated decreased NSS, infarction volume and FJB positive cells as well as p-S6 expression in the penumbra area (P<0.05 or P<0.01). There was no significant difference between the groups of rapamycin administrated 6 h and 24 h after modeling (all P>0.05).
Conclusions: Rapamycin treatment starting at 24 h after I/R exhibits protective effect on brain injury in rats.
目的: 探讨雷帕霉素在大鼠局灶性脑缺血再灌注后24 h给药对脑损伤的保护作用。
方法: 104只Sprague Dawley大鼠随机分为手术对照组、模型对照组、建模后6 h雷帕霉素给药组（6 h给药组）和建模后24 h雷帕霉素给药组（24 h给药组）。采用Longa法建立大鼠大脑中动脉缺血再灌注模型。采用神经功能损伤程度评分（NSS）对大鼠进行神经功能评分；氯化三苯基四氮唑（TTC）染色法检测各组大鼠脑梗死体积；Fluoro-Jade B（FJB）染色法检测大鼠脑组织神经元凋亡；蛋白质印迹法检测各组大鼠mTOR信号通路磷酸化S6蛋白表达。
结果: 与手术对照组比较，模型对照组大鼠NSS升高，脑梗死体积增加，FJB阳性细胞增多，半暗带磷酸化S6蛋白表达量增加（均 P < 0.01）；与模型对照组比较，6 h和24 h给药组大鼠NSS均降低，脑梗死体积缩小，FJB阳性细胞减少，半暗带磷酸化S6蛋白表达量减少（均 P < 0.05或 P < 0.01），且24 h给药组各项指标变化与6 h给药组差异均无统计学意义（均 P > 0.05）。
结论: 缺血再灌注后24 h给予雷帕霉素对大鼠局灶性脑缺血再灌注所致脑损伤仍有保护作用。