甘珀酸对大鼠局灶性脑缺血后神经元损伤的影响

The Effect of Carbenoxolone on Neurons Injury after Focal Cerebral Ischemia

目的探讨缝隙连接阻断剂甘珀酸对大鼠局灶性脑缺血后神经元损伤的影响。方法成年雄性Sprague-Dawley大鼠70只随机分为对照组(n=30)、药物组(n=30)和假手术组(n=10)。药物组术前2h左侧脑室注射缝隙连接阻断剂甘珀酸,对照组左侧脑室注射0.9%氯化钠溶液,颈内动脉插线法制备大鼠大脑中动脉缺血-再灌注模型。术后24h,采用干湿重法检测脑组织水肿程度,红四氮唑(TTC)染色法测量脑梗死体积,并进行神经功能评分;术后3d,采用DNA原位末端标记TUNEL技术观察大鼠海马迟发性神经元死亡,以观察甘珀酸对局灶性脑缺血后不同时间及不同区域神经元损伤的影响。结果与对照组比较,药物组大鼠术后神经功能评分低,脑水肿程度轻,梗死体积小(P<0.01)。不给予甘珀酸,大脑中动脉缺血模型有50%大鼠在术后3d出现海马迟发性神经元死亡;用甘珀酸阻断缝隙连接通讯后,20%的大鼠出现海马迟发性神经元死亡,其发生率明显减小(P<0.05)。结论甘珀酸对局灶性脑缺血后神经元具有保护作用。

Objective To explore the effect of carbenoxolone on neurons injury after focal cerebral ischemia. Methods A rat model of middle cerebral artery occlusion and reperfusion was made by the intraluminal occlusion technique. 70 SD rats were randomly divided into control group, drug treated group and sham operated group, 10 rats in each. Carbenoxolone, a gap junction blocker, was injected on left side of cerebral ventricle 2 h before operation. Rats in the control group were injected with N.S. in the same route. All the rats were valuated by the behavior scores, brain edema and infarct volume 24 h after the operation. TUNEL staining was used to detect the delayed neuronal death in hippocampus 3 d after ischemia. Results Compared with the control group, the behavior scores, brain edema, infarct volume and rate of delayed neuronal death were significantly decreased （P 〈 0.01 ） in the experimental group. 50% of rats without carbenoxolone developed delayed neuronal death 3 d after operation, while only 20% in carbenoxolone treated rats. The incidence of delayed neuronal death was markedly abated（ P 〈 0.05 ）. Conclusion Carbenoxolone can protect neurons after focal cerebral ischemia.