参芎化瘀胶囊对全脑缺血再灌注大鼠神经细胞凋亡的影响

Effect of Shenxionghuayu capsule on neuronal apoptosis after global cerebral ischemia reperfusion in rats

目的：探讨参芎化瘀胶囊对脑缺血再灌注损伤后神经细胞凋亡的影响.方法：雄性SD大鼠随机分成假手术组,模型组,参芎化瘀胶囊高、低剂量组.改良的Pulsineli 4血管阻断（4-VO）法制作全脑缺血模型.术后尼氏染色观察海马区神经细胞组织形态变化,免疫组织化学法和免疫印记法检测海马区血管内皮生长因子（VEGF）蛋白的表达,原位缺口末端标记法（TUNEL）检测凋亡细胞,术后3～7d水迷宫法测试动物学习记忆功能.结果：与假手术组比较,模型组中海马神经元结构损伤明显,VEGF表达及凋亡神经细胞数量增加;动物搜索安全岛潜伏期延长;与模型组比较,神经元形态结构损伤减轻、神经细胞凋亡数量下降、VEGF表达进一步增加,动物搜索安全岛潜伏期缩短;上述变化在高剂量参芎化瘀胶囊组更为明显.结论：参芎化瘀胶囊对脑缺血再灌注损伤有治疗作用,其机制与调控VEGF表达、抑制神经细胞凋亡有关.

Objective： To investigate the effects of Shenxionghuayu capsule on neuronal apoptosis and its underlying mechanism after cerebral ischemia reperfusion. Methods： Male Sprague-Dawley rats were divided randomly into four groups： sham group, model group, low and high dose of ShenrSonghuayu capsule treatment groups. Cerebral ischemia model was formed by improved four-vessel occlusion according to the description of Pulsinelli＇s method. Morphological changes in hippocampal region were observed by Nissl staining; The vascular endothelial growth factor （VEGF） expression was detected by immunohistochemistry and Western blot; The apoptotic cells was measured with TUNEL method; Learning and memory function （Morris water maze） was performed daily from 3d to 7d after injury. Results： Compared with the sham group, neuronal morphous was damaged, the VEGF expression and the number of neural apoptotic cells enhanced and latency of finding the platform prolonged in the model group; Compared with the model group, the morphological damage of brain tissue and the number of neural apoptotic cells decreased obviously, the VEGF expression increased, the latency of finding the platform were shorten. These changes were more obvious in the high dose of Shenxionghuayu capsule group. Conclusion： Shenxionghuayu capsule have therapeutic effect following forebrain ischemia-reperfusion injury and the molecular mechanism is related to regulate VEGF expression and attenuate neuronal apoptosis.