目的 探讨心搏骤停心肺复苏后溶栓药物尿激酶对脑神经细胞凋亡的影响。方法 20只家兔按随机数字表法被分为溶栓组和常规复苏组,每组10只。采用氯化钾注射法结合窒息法致心搏骤停后,常规复苏组只进行心肺复苏及基本生命支持,溶栓组在此基础上给予尿激酶2万U/kg进行干预。通过细胞凋亡原位检测(Tunel),免疫组织化学法检测半胱天冬蛋白酶-3(caspase-3)以此来证明尿激酶对脑神经细胞凋亡的影响。结果 溶栓组复苏24 h后大脑皮质和海马Tunel和 Casepase-3阳性细胞均明显低于常规复苏组,Tunnel:皮质29.22±7.86比37.20±7.04(t=-2.392,P=0.028),海马18.80±7.58比27.4±8.15(t=-2.442,P=0.025),Caspase-3:皮质22.1±9.93比33.1±12.64(t=-2.165,P=0.044),海马31.3±15.23比46.8±16.73(t=-2.167,P=0.044),差异有统计学意义。常规复苏组与溶栓组自主循环恢复时间(s)、自主呼吸恢复时间(min)、平均动脉压(mmHg,)均无明显差异[自主循环恢复时间:307.9±96.4比242.0±71.0(t=-1.741,P=0.099),自主呼吸恢复时间:20.6±12.5比19.3±10.0(t=-0.256,P=0.801),平均动脉压:65.5±6.2比69.0±6.7(t=1.217,P=0.239)]。结论 心脏骤停后在心肺复苏时给予溶栓药物尿激酶可以改善并减轻因细胞凋亡所致脑神经损害。
Abstract
Objective To investigate the effect of urokinase on nerve cell apoptosis after cardiac arrest(CA) and cardiopulmonary resuscitation(CPR)in rabbits. Methods 20 rabbits were randomly divided into experimental group and control group, 10 rabbits in each group. Potassium chloride injection combined with asphyxia method was conducted to establish the CA models. CPR and basic life-support were performed in experimental group. Based on above treatments, intervention with urokinase (20 000 U/kg) was conducted in experimental group. Neural apoptosis was identified by TUNEL and caspase-3 was detected by immunohistochemistry in order to prove the effect of urokinase on nerve cell apoptosis in rabbits 24 hours after CPR. Results Tunel and caspase-3 positive cells counts of cerebral cortex and hippocampus in experimental group were significantly less than those in control group, respectively. The comparisons were as follows(Tunel positive cells in cerebral cortex 29.22±7.86: 37.20±7.04(t=-2.392,P=0.028), in hippocampus 18.80±7.58: 27.4±8.15(t=-2.442,P=0.025), Caspase-3 positive cells in cerebral cortex 22.1±9.93:33.1±12.64(t=-2.165,P=0.044),in hippocampus 31.3±15.23 vs 46.8±16.73(t=-2.167,P=0.044); so thrombolytic therapy with urokinase can relieve nerve cell apoptosis obviously. Comparison of spontaneous circulation restoration time(s) 307.9±96.4: 242.0±71.0(t=-1.741, P=0.099), spontaneous breathing restoration time(min) 20.6±12.5:19.3±10.0 (t=-0.256, P=0.801), mean arterial pressure MAP (mmHg) 65.5±6.2: 69.0±6.7 (t=1.217, P=0.239), there were no differences between the experimental group and control group. Conclusions Thrombolytic therapy with urokinase in CPR after CA can improve and lessen nervous lesion resulting from apoptosis in rabbits.
关键词
心肺复苏 /
尿激酶 /
溶栓 /
神经细胞凋亡
Key words
cardiopulmonary resuscitation /
cardiac arrest /
urokinase, caspase-3 /
Tunel /
nerve cell apoptosis
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基金
全军医学科技“十二五”课题计划(BWS11J077);武警总医院一类课题(WZ2008001)
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