单唾液酸神经节苷脂对大鼠体外循环脑损伤的影响

Effect of GM-1 on Brain Injury Associated-CPB in Rats

目的：单唾液酸神经节苷脂（GM-1）是神经细胞膜上的一种鞘糖脂，参与多种生理功能，具有抗氧化和神经保护作用，本课题主要探讨单唾液酸神经节苷脂对大鼠体外循环（CPB）脑损伤的影响。方法：成年雄性SD大鼠30只，14月龄，体重300-400g，采用随机数字表法，将大鼠随机分成3组（n=10）：假手术组（s组）、CPB组和GM-1组。采用右颈静脉腔房引流，右颈动脉灌注法建立大鼠CPB模型。CPB组和GM-1组行CPB1h，其中CPB组转流液中加入GM-120mg／kg，GM-1组给予等容量的生理盐水。CPB结束后3h和s组机械通气结束后3h时，断头取左侧脑组织，透射电镜下观察海马超微结构变化；TUNEL法检测海马神经元调亡情况。结果：电镜下CPB组海马可见异染色质明显边集、凝聚，线粒体嵴减少或空泡变性，细胞器消失等不可逆性的损伤改变；GM-1组神经元细胞核圆形，线粒体嵴少量减少，细胞器仍可见。与S组比较，CPB组和GM-1组海马神经元病理损伤严重，且凋亡神经元明显增多（P〈0．05）。与CPB组相比，GM-I组海马神经元病理损伤减轻，且凋亡神经元有所减少（P〈0．05）。结论：体外循环可导致以大鼠海马神经元超微结构发生改变为标志的脑损伤，GM-1可减轻CPB诱发的脑损伤，其机制可能与其抑制神经元凋亡有关。

Objective： Ganglioside （GM-1） is a glycosphingolipid present in most cell membranes, displaying antioxidant, neuroprotective properties, and participated in multiple physiological function.To investigate the effect of GM-I on brain injury associated-CPB in rats. Methods： Twenty-seven fourteen-month-old adult male SD rats weighing 300 to 400 g were randomly divided into 3 groups （n=10 each）： group I Sham; group 1I CPB; group IIIGM-1. Experimental model of CPB in rats was established via left carotid and right jugular vein caunulation for arterial perfusion and venous return respectively. In group CPB and group GM-1 the rats underwent lh CPB; group CPB in which saline （1 mg/kg） was administrated for priming liquid; group GM-1 in which GM-1 （20 mg/kg） was administrated for priming liquid Samples of left were collected at 3h after CPB. Electron microscopy technique was used to observe ultrastructure of the hippocampus and neuron apoptosis were quantitatively examined with TUNEL method. Results： Electron microscopy showed that there were heterochromatin marginating, vacuolar degeneration or cristae disappearing of mitochondria, cell organelles disappearing in CPB group and in GM-1 group there were nucleus round, a little disappeared cristae of mitochondria and organelles were still visible. Compared with group S, the apoptosis of nerve cells increased significantly, while the ultrastructural changes obviously under the transmission electron microscope in group CPB and group GM-1 （P〈0.05）. Compared with group CPB, the apoptosis of nerve cells decreased significantly, while the injury degree of ultrastructural increased not significantly in group GM-1 （P〈0.05）. Conclusions： Ultra-structural changes consistent with apoptosis occurred in neurone of rat with cardiopulmonary bypass. GM-1 can attenuate cerebral injury associated-CPB, maybe due to the reduction of neuronal apoptosis.