神经节苷脂-1与康复训练对缺血缺氧性脑损伤大鼠神经功能的影响

Effect of Ganglioside-1 and Rehabilitation on Recovery of Neurologic Behavior in Rats with Hypoxic-ischemic Brain Damage

目的探讨神经节苷脂-1(GM1)和康复训练对大鼠缺血缺氧性脑损伤(HIBD)后功能恢复的影响及可能机制。方法 48只Sprague-Dawley幼鼠建立HIBD模型,分为对照组、GM1组、康复训练(R)组、GM1+康复训练(GM1+R)组及假手术组。各组大鼠采用悬吊试验、斜坡试验和水迷宫试验进行评定。免疫组化法检测海马、额叶皮质神经元活化型caspase-3表达。结果各组间悬吊试验、斜坡试验结果有非常高度显著性差异(P<0.001),从高到低依次为假手术组、GM1+R组、R组、GM1组和对照组(P<0.05)。各组间寻找平台潜伏期有非常显著性差异(P<0.01),对照组和GM1组较假手术组长(P<0.05)。GM1组和R组的海马、额叶皮质活化型caspase-3水平与假手术组有显著性差异(P<0.05),GM1组、R组及GM1+R组海马活化型caspase-3与对照组有显著性差异(P<0.05),R组和GM1+R组额叶皮质活化型caspase-3与对照组有显著性差异(P<0.05)。海马、额皮质活化型caspase-3的表达与悬吊试验、斜坡试验结果正相关(P<0.05),与水迷宫试验无明显相关(P>0.05)。结论早期康复训练及应用GM1对HIBD神经功能恢复有一定疗效,联合应用存在协同效应。其机制可能与神经元末梢突触后存在大量活化型caspase-3有关。

Objective To investigate the effects and the possible mechanism of Ganglioside-1 （GM1） and rehabilitation on neurologic behaviors of rats with hypoxic-ischemic brain damage （HIBD）. Methods 48 immature rats developed as model of HIBD were divided into 5 groups： control group, GM1 group, rehabilitation training group （R group）, GM1＋R group, and sham group. They were evaluated with Climb, Slope and Water Maze Tests. The expressions of activated caspase-3 in neurons were detected with immunohistochemistry. Results The achievement of Climb and Slope Test were significantly different among groups （P〈0.001）, which ranked as the sham group〉GM1＋R group〉R group〉GM1 group〉control group （P〈0.05）. The latency of Water Maze Test was significantly different among groups （P〈0.01）, which was longer in the control and GM1 groups than in the sham group （P〈0.05）. The activated caspase-3 expressed in hippocampus and frontal cortex was less in the GM1 and R groups than in the sham group （P〈0.05）, more in the GM1 group, R group and GM1＋R group than in the control group in hippocampus （P〈0.05）, more in the R group and GM1＋R group than in the control group in frontal cortex （P〈0.05）. The expression of activated caspase-3 in both hippocampus and frontal cortex correlated with the achievement of Climb and Slope Test （P〈0.05）, but not with the latency of Water Maze Test （P〉0.05）. Conclusion Rehabilitation training and GM1 are effective on recovery of neu-ral function in rats with HIBD with synergia, which may associated with the activated caspase-3 in terminal synapse.