单唾液酸神经节苷脂对体外循环诱发大鼠脑损伤的影响

Effect of monosialoganglioside GM-1 on cardiopulmonary bypass-induced brain injury in rats

目的评价单唾液酸神经节苷脂（GM-1）对体外循环（CPB）诱发大鼠脑损伤的影响。方法成年雄性SD大鼠27只，15月龄，体重350～450g。采用随机数字表法，将大鼠随机分为3组（n=9）：对照组（C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GM-1组预充液中加入GM-120mg／kg，CPB组给予等容量的生理盐水。CPB结束后3h和C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；免疫组化和Westernblot法检测Bax和Bcl-2蛋白表达水平。结果与C组比较，CPB组和GM-1组凋亡神经元增多，Bax和Bcl-2蛋白表达上调，Bax／Bcl-2比值升高（P〈0．05）；与CPB组比较，GM-1组凋亡神经元减少，Bax蛋白表达下词，Bcl-2蛋白表达上调，Bax／Bcl-2比值降低（P〈0．05）。CPB组海马神经元病理损伤严重，GM-1组海马神经元病理损伤减轻。结论GM-1可减轻CPB诱发大鼠脑损伤，其机制可能与其抑制神经元凋亡有关。

Objective To investigate the effect of monosialoganglioside GM-1 on cardiopulmonary bypass （CPB）-induced brain injury in rats. Methods Twenty-seven adult male Sprague-Dawley rats, weighing 350- 450 g, aged 15 months, were randomly divided into 3 groups （ n = 9 each） ： control group （C group）, CPB group and GM-I group. The animals were anesthetized with chloral hydrate, traeheostomized and mechanically ventilat- ed. Right common carotid and right jugular vein were cannulated for closed-chest CPB. In groups CPB and GM-1, the rats underwent 1 h CPB. GM-I 20 mg/kg was added to the priming solution in group GM-1, while the equal volume of normal saline was given in group CPB. The animals were sacrificed at 3 h after termination of CPB or 3 h after the end of ventilation in group C, the brains were removed and the hippocampi isolated for microscopic ex- amination and for determination of apoptosis （ using TUNEL） and Bax and Bcl-2 protein expression （by immunohis- tuchemistry and Western blot）. Results Compared with group C, the number of apoptotic neurons and ratio of Bax/Bcl-2 were significantly increased, and the expression of Bcl-2 and Bax protein was up-regulated in groups CPB and GM-I （ P 〈 0.05）. Compared with group CPB, the number of apoptotic neurons and ratio of Bax/Bcl-2 were significantly decreased, the expression of Bax protein was down-regulated and the expression of Bcl-2 protein was up-regulated in group GM-1. The pathological changes were severe in group CPB and attenuated in group GM-1. Conclusion GM-I can attenuate CPB-induced brain injury in rats and inhibition of the apoptosis in neurons may be involved in the mechanism.