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目的旨在探讨肢体缺血预处理(LIP)能否减轻脑缺血过程中海马CA1区神经元凋亡和脑水肿。方法72只永久凝闭椎动脉的Wistar大鼠随机分为6组:假手术,LIP(双侧股动脉夹闭10min,间歇10min,3次循环),脑缺血,LIP+脑缺血,DMSO和SB 203580+LIP+脑缺血组。各组大鼠中6只在脑缺血后3d处死,TUNEL染色计数凋亡细胞;6只在脑缺血后24h处死,测定脑组织含水量。结果TUNEL染色显示,假手术和LIP组海马CA1区偶有TUNEL阳性细胞;脑缺血组海马CA1区可见大量棕黄色着色的TUNEL阳性细胞,与假手术组及LIP组相比,细胞数量明显增加;LIP+脑缺血组,TUNEL阳性神经元数与脑缺血组相比明显减少,提示LIP明显抑制缺血引起的海马CA1区锥体细胞凋亡;有丝分裂原激活蛋白激酶p38拮抗剂SB 203580+LIP+脑缺血组,海马CA1区阳性染色锥体细胞明显增加,与DMSO+LIP+脑缺血组相比有显著性差别,表明SB 203580可拮抗LIP抑制凋亡的作用。与假手术和LIP组比较,脑缺血组脑组织含水量明显增加,表明LIP降低了脑缺血引起的脑组织含水量增加;LIP前应用SB 203580可抑制LIP的脑保护作用,使脑组织含水量较LIP+脑缺血组显著增加。结论LIP能够减轻脑缺血过程中海马CA1区神经元凋亡和脑水肿,可能与活化有丝分裂原激活蛋白激酶p38有关。
Objectives To investigate whether limb ischemic preconditioning (LIP) attenuates neuronal apoptosis and cerebral edema in hippocampal CA1 region during cerebral ischemia. Methods Seventy-two Wistar rats with permanent vertebral artery occlusion were randomly divided into 6 groups: sham operation, LIP (bilateral femoral artery occlusion 10 min, intermittent 10 min, 3 cycles), cerebral ischemia, LIP + cerebral ischemia, DMSO and SB 203580 + LIP + cerebral ischemia group. Six rats in each group were killed 3 days after cerebral ischemia, and apoptotic cells were counted by TUNEL staining. Six rats were sacrificed 24h after cerebral ischemia, and the water content of brain tissue was measured. Results TUNEL staining showed that there were occasional TUNEL positive cells in hippocampal CA1 region of sham-operation group and LIP group. A large number of TUNEL-positive cells were observed in hippocampal CA1 area of hippocampus. Compared with sham operation group and LIP group, ; LIP + cerebral ischemia group, the number of TUNEL-positive neurons was significantly decreased compared with cerebral ischemia group, suggesting that LIP significantly inhibited ischemia-induced apoptosis of pyramidal cells in CA1 pyramidal neurons; mitogen-activated protein kinase p38 antagonist SB 203580 + Compared with DMSO + LIP + cerebral ischemia group, LIP + cerebral ischemic group and hippocampal CA1 positive staining pyramidal cells significantly increased, indicating that SB 203580 can antagonize the inhibitory effect of LIP on apoptosis. Compared with the sham group and the LIP group, the water content of brain tissue in the ischemic group increased significantly, indicating that LIP reduced the water content of brain tissue induced by cerebral ischemia; SB 203580 before LIP could inhibit the brain protective effect of LIP, Water content than LIP + cerebral ischemia group increased significantly. Conclusion LIP can attenuate neuronal apoptosis and cerebral edema in CA1 hippocampus during cerebral ischemia, which may be related to the activation of mitogen-activated protein kinase p38.