摘要
目的比较尼莫地平2种给药途径对兔蛛网膜下腔出血（SAH）后海马线粒体通路的影响。方法24只新西兰大白兔按照随机数字表法分为假手术组、SAH组、尼莫地平静脉组（ND1组）、尼莫地平枕大池组DJD2组），每组6只。后3组兔麻醉后取自体动脉血（1mL／kg）注入枕大池制作SAH模型，假手术组注入等量生理盐水；30min后ND2组再次经枕大池注入0．5mL／kg0．2％尼莫地平，假手术组、SAH、ND1组则注入等体积生理盐水；同时NDl组经静脉注入0．5mL／kg0．2％尼莫地平，假手术组、SAH、ND2组注入等体积生理盐水。造模后72h对兔进行摄食量和神经功能损害分级并处死动物，取海马组织采用RT—PCR及Westernblotting技术检测半胱氨酸天冬氨酸蛋白酶3（Caspase-31、细胞色素C（Cyt-c）mRNA及蛋白表达。结果4组动物造模后72h摄食量及神经功能损害差异均有统计学意义（H=16．664，P=-0．001；H=15．411，P=-0．001）；平均秩次提示，ND2组动物摄食量下降及神经功能损害程度较ND1组动物轻。4组动物海马组织Caspase-3、Cyt-c mRNA及蛋白相对表达量差异有统计学意义（P〈0．05），与SAH组比较，ND1、ND2组Caspase-3、Cyt-c mRNA及蛋白相对表达量明显降低，差异有统计学意义（P〈0．05）；与ND1组比较，ND2组Caspase-3、Cyt—CmRNA及蛋白相对表达量明显降低，差异有统计学意义（P〈0．05）。结论等剂量尼莫地平经枕大池注入比静脉注入能更有效地降低Caspase-3、Cyt-c表达，抑制海马线粒体通路激活。
Objective To compare the effects of two methods of nimodipine administration on mitochondrial pathway in the hippocampus of rabbit models of subarachnoid hemorrhage. Methods Twenty-four New Zealand white rabbits were randomly allocated to sham-operated group, subarachnoid hemorrhage （SAH） group and nimodipine introvenous injection （ND1） group, and nimodipine intracisternal administration （ND2） group （n=6）. All animals underwent operation under anaesthesia; one mL/kg autologous nonheparinized arterial blood was injected into cisterna magna in SAH group, ND1 and ND2 group, and one mL/kg saline into cisterna magna in sham-operated group. Thirty minutes after SAH, 0.5 mL/kg 0.2% nimodipine was injected into cistema magna in ND2 group, and equal-volume saline into cisterna magna in sham-operated group, SAH group and ND1 group. While 0.5 mL/kg 0.2% nimodipine via introvenously injection was performed in the ND1 group, and equal-volume saline via introvenously injection into the sham-operated group, SAH group and ND2 group. All animals were assessed for the grading of food intake and neurological impairment 72 h after SAH, and then, they were scarified; their hippocampi were processed for detecting the mRNA and protein expressions of Caspase-3 and Cyt-c by using real time-PCR and Western blotting. Results The differences of food intake and neurological impairment between the four groups were statistically significant 72 h after SAH （H=16.664, P=0.001; H=15.411, P=0.001）; according mean rank, the food intake and neurological impairment in the ND2 group were decreased as compared with those in the ND2 group. The mRNA and protein expression levels of Caspase-3 and Cyt-c among the four groups were statistically different （P〈0.05）. As compared with those in the sham-operated group and SAH group, the mRNA and protein expression levels of Caspase-3 and Cyt-c were significantly higher in the ND1 and ND2 groups （P〈0.05）; As compared with ND1 group, ND2 group had significantly lower mRNA and protei
出处
《中华神经医学杂志》
CSCD
北大核心
2017年第8期790-795,共6页
Chinese Journal of Neuromedicine
基金
贵州省科技计划项目[黔科合基础（2016）1095]
关键词
尼莫地平
给药途径
蛛网膜下腔出血
线粒体通路
细胞凋亡
Nimodipine
Administration method
Subarachnoid hemorrhage
Mitochondrial pathway
Apoptosis
