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目的:探讨缺血前给予自噬诱导剂对脑缺血损伤的保护效应及可能机制。方法:双侧颈总动脉结扎建立全脑缺血模型,再灌注后24 h,评价动物神经行为功能,连续脑切片,采用Nissl染色定量检测皮层及海马CA1区细胞密度;通过免疫荧光技术检测Caspase-3阳性神经元,计数皮层及海马CA1凋亡细胞数量;激光共聚焦显微镜观察并计数海马齿状回颗粒下层内呈Ki67阳性、GFAP(胶质纤维酸性蛋白)阴性(Ki67+/GFAP-)细胞的数量。结果:Rapamycin术前预处理可以改善缺血导致的神经功能缺陷(P<0.05)。Nissl染色结果表明Ra-pamincy术前1 h给药可以减轻缺血导致的皮层(P<0.01)及海马CA1区(P<0.01)细胞丢失。同时,Rapamycin术前给药也显著减少了缺血导致的皮层及海马CA1区内Caspase-3阳性细胞的数量,组间比较有显著性差异(P<0.05)。Rapamycin术前1 h给药增加了海马齿状回内Ki67+/GFAP-细胞的数量,和缺血组比较差异有显著性(P<0.05)。结论:在全脑缺血模型上,通过自噬活化途径的缺血预处理可以保护缺血性脑损伤,这一作用和Rapamycin减少凋亡、增加新生神经细胞的数量有关。
Objective: To investigate the protective effect and possible mechanism of autophagy-inducing agent on cerebral ischemic injury before ischemia. Methods: The model of global cerebral ischemia was established by ligation of bilateral common carotid arteries. Neurobehavioral function and neurological function of animals were evaluated 24 h after reperfusion. Nissl staining was used to detect the cell density of cortex and hippocampal CA1 region. Caspase -3 positive neurons were counted and the number of apoptotic cells in cortex and hippocampal CA1 were counted. The number of apoptotic cells in CA1 of cortex and hippocampus was counted by laser scanning confocal microscopy. Ki67 positive and GFAP negative (Ki67 + / GFAP-) cells quantity. Results: Rapamycin preconditioning could ameliorate ischemic neurological deficits (P <0.05). Nissl staining showed that administration of Ra-pamincy 1 h before ischemia could reduce ischemia-induced cortical (P <0.01) and hippocampal CA1 (P <0.01) cell loss. Meanwhile, preoperative administration of Rapamycin also significantly reduced the number of Caspase-3 positive cells in cortex and hippocampal CA1 region induced by ischemia, with significant difference between the two groups (P <0.05). Administration of Rapamycin 1 h before surgery increased the number of Ki67 + / GFAP- cells in the hippocampal dentate gyrus, which was significantly different from that in the ischemic group (P <0.05). CONCLUSION: Ischemic brain injury can be protected by ischemic preconditioning via an autophagic activation pathway in a rat model of global cerebral ischemia, which is related to the reduction of apoptosis and the number of newborn neurons by rapamycin.