神经节苷脂GM_1对大鼠急性脑损伤后神经细胞凋亡的抑制作用

The inhibiting effect of ganglioside GM_1 on nerve cell apoptosis after traumatic brain injury in the rats

目的观察外源性GM1对大鼠急性脑损伤修复的影响,探讨其与神经细胞凋亡发生、发展的关系。方法落体撞击法造成大鼠左顶叶局限性脑挫裂伤。将65只大鼠分为假手术组、脑损伤组和给药组。分别于损伤后或损伤并给药后2、6、12、24、48、168 h时用免疫组化染色观察脑皮质细胞Bcl-2、Bax蛋白表达及PARP降解,TUNEL法观察脑皮质细胞凋亡的情况。结果给药组大鼠损伤侧Bcl-2表达在给药后12 h增至最大,随后逐渐降低,168 h时降低至与假手术组相近。而Bax表达在给药后24 h下调最大,给药后损伤侧Bax/Bcl-2比值均有下降,其中12 h时的降幅较大,24 h后二者比值趋于正常。PARP降解从12 h后开始下调,凋亡细胞减少。结论给药后Bax/Bcl-2比值下降,PARP降解下调,凋亡细胞减少,表明GM1对急性脑损伤后神经细胞凋亡具有抑制作用。

OBJECTIVE To investigate the repairing effect of ganglioside GM： and the relevant involving mechanism of neuronal apoptosis after the traumatic brain injury in the rats. METHODS 65 Wistar rats were randomly divided into 3 groups ： sham - opera- tion group （ n = 5 ） , brain injury group （ n = 30 ）, GMI group （ n = 30）. Local contusion and laceration of the left parietal lobe of the rat brain was induced by the impact of an object （50 g）dropping from 10 cm above the head. The rats were killed at 2,6,12,24,48 and 168 hours after the injury, respectively, and take the samples for expression of Bax and Bcl -2 protein and detection of PARP degrada- tion with immunohistochemical method. TUNEL histochemistry was used to identify DNA fragmentation. RESULTS In GM1 group,the level of Bcl -2 protein expression occurred a peak at 12 h pose -injury, while that of bax protein expression appeared at the nadir 24 h pose - injury. The ratio of Bax/Bcl - 2 decreased significantly in comparison to brain injury group. The PARP degradation began to reduce at 12 h following the injury and nerve cell apoptosis lessened. CONCLUSION The therapy of GM1 may decrease the ratio of Bax/Bcl -2 and reduced the PARP degradation, and inhibit nerve cell apoptosis.