超早期和早期运动训练对脑梗死大鼠神经功能恢复的影响及机制

Effects and mechanism of very early and early exercise training on the recovery of neural function in rats with acute cerebral infarction

目的:探讨超早期和早期运动训练对脑梗死急性期大鼠神经功能恢复的影响及梗死边缘区皮质神经细胞坏死及凋亡在其中的作用。方法:将成年雄性SD大鼠104只,采用改良Zea-Longa线栓法制作左侧大脑中动脉阻塞再灌注模型,随机分为5组:超早期训练组(31只)、早期训练组(22只)、超早期对照组(23只)、早期对照组(23只)、假手术组(5只)。训练组大鼠分别于术后24h、48h开始每天予以跑笼运动训练;对照组和假手术组大鼠置于普通笼内饲养,不予以任何针对性训练。各组大鼠在造模术后24h、运动训练前和运动训练第14d分别进行神经功能评分。训练3d后检测脑组织含水量,训练14d后检测梗死体积并采用尼氏染色、TUNEL法分别观察脑皮质梗死边缘区细胞坏死、凋亡的情况。结果:随机分组后,超早期训练组的死亡率高于早期训练组的死亡率(41.94%vs 18.18%)。训练第14d,早期训练组的mNSS评分均明显优于其对照组(P<0.05);早期组(训练组-对照组)mNSS评分差值与超早期组mNSS评分差值之间比较有显著性差异(P<0.05)。训练3d后,超早期训练组的脑组织含水量较其对照组明显增加(P<0.05);早期训练组的脑组织含水量较其对照组无明显差异(P>0.05)。训练14d后,超早期训练组的脑梗死体积与其对照组比较无明显差异(P>0.05);早期训练组的脑梗死体积均明显小于其对照组(P<0.05);各训练组与相应的对照组梗死体积的比值示早期组小于超早期组(P<0.05)。超早期训练组梗死边缘区的神经细胞数量、TUNEL阳性细胞数与其对照组相比无明显差异(P>0.05);早期训练组梗死边缘区的神经细胞数量明显多于其对照组(P<0.05),TUNEL阳性细胞数较其对照组明显减少(P<0.05)。结论:早期运动训练与超早期运动训练相比,可以显著改善急性脑梗死大鼠的神经功能,其机制可能与减少梗死边缘区神经细胞的坏死与凋亡有关。

Objective： To investigate effects of very early and early exercise training on neurological function and the role of neural necrosis and apoptosis in cortex of peri-infarct region in rats with acute cerebral infarction. Method： A total of 104 male Sprague-Dawley（SD） rats after transient left middle cerebral artery occlusion（tM-CAO） were randomly divided into five groups： very early exercise group（31 rats）, early exercise group（22 rats）, very early control group（23 rats）, early control group （23 rats）, sham-operated group（5 rats）. Exercise group were exposed to the wheel running from 24h, 48h after stroke respectively. The control group and sham group were fed in cages with no any special training exercise. The neurological functions were tested by modified neurological severity scores （mNSS） at 24h after tMCAO, before training and 14d after training exercise. The rats in each group were sacrificed at 24h after tMCAO and 3d,14d after training exercise. The brain water content and the infarction volumes were calculated. And the neural necrosis, apoptosis in the peri-infarction region were observed through Nissl staining and TUNEL method. Result： After random grouping, the mortality rate in the very early exercise training group was higher than that in the early exercise training group （41.94% vs 18.18%）. The rats in early exercise group showed significantly better neurological function than corresponding control group （P〈0.05）. The values of difference mNSS score （exercise group-control group） in early group was significantly different that in very early group （P〈 0.05）. After 3 days exercise,the brain water content of rats in very early exercise group was significantly more than corresponding control group （P〈0.05）. Early exercise group was not significantly different that corresponding control group （P〉0.05）. After 14 days exercise,the infarction volumes of rats in very early exercise group was not significantly different compared with corresponding control group （P〉0.05）. The infarction volumes of rats in early exercise group was significantly less than corresponding control group （P〈0.05）. The values of relative infarct volume in early exercise group was lower than that in very early exercise group （P〈0.05）. Both the Nissl staining and the TUNEL results showed that very early exercise group was not significantly different with that of corresponding control group （P〉0.05）, while the number of neural cells of early exercise group was much more than that of corresponding control group （P〈0.05）. and the number of TUNEL positive cells of early exercise group was much less than that of corresponding control group （P〈0.05）. Conclusion： Early exercise training, compared with very early exercise training, can significantly improve the neurological function of rats with acute cerebral infarction. The mechanism may be associated with the reduction of necrosis and apoptosis of in cortex of peri-infarct region.