中文摘要：

目的探讨线粒体分裂抑制剂1（mdivi-1）在复苏后大鼠脑损伤中的作用及其机制。方法将50只健康成年雄性SD大鼠按随机数字表法分为假手术组（Sham组，n=8）、心搏骤停模型组（CA组，n=14）、二甲基亚砜对照组（DMSO组，n=14）和mdivi-1组（n=14）。以窒息法诱导大鼠CA后进行心肺复苏（CPR）；自主循环恢复（ROSC）后，mdivi-1组静脉注射1．2mg／kgmdivi-1进行干预，DMSO组注射等体积0．1％DMSO。复苏后24、48和72h，对各组大鼠进行神经功能缺损评分（NDS）；复苏后72h留取各组大鼠脑组织，苏木素-伊红（HE）染色，观察海马组织病理学改变，并计数正常神经元；采用原位末端缺刻标记法（TUNEL）检测海马组织神经元凋亡；采用蛋白质免疫印迹试验（WesternBlot）检测线粒体和胞质中细胞色素c（Cyt—C）蛋白表达。结果各实验组复苏后NDS评分逐渐升高；CA组复苏24、48、72hNDS评分较Sham组明显降低（分：51．5±3．7比80．0±0．0，59.3±3．6比80．0±0．0，66．7±2．6比80．0±0．0，均P〈0．05）；海马CA1区正常椎体神经元明显减少（个／HP：4．4±1．1比23．1±4．0，P〈0．05），神经元凋亡指数明显增加[（86．9±6．9）％比（3．4±0．8）％，P〈0．05]，线粒体Cyt—C表达明显减少（A值：0．46±0．18比1．00±0．00，P〈0．05），胞质Cyt—C表达明显增加（A值：6．65±0．21比1．00±0．00，P〈0．05）。Mdivi-1组复苏后24h和48hNDS评分较CA组有所提高（分：55．2±3．3比51．5±3．7，64．7±2．4比59．3±3．6，但均P〉0．05），72h时NDS评分明显提高（分：74．5±2.3比66．7±2．6，P〈0．05）；海马CA1区正常椎体神经元明显增加（个／HP：16．2±2．4比4．4±1．1，P〈0．05），神经元凋亡指数明显降低[（42．3±3．9）％比（86．9±6．9）％，P〈0．05]，线粒体Cyt—C表达明显增加（A值：0．83±0．22比0．46±0．

英文摘要：

Objective To investigate the effects of mitochondrial division inhibitor 1 （mdivi-1） in rats after cardiopulmonary resuscitation （CPR） and its mechanism. Methods Fifty Spragne-Dawley （SD） rats were randomly （random number table） divided into sham group （n = 8）, cardiac arrest （CA） model group （n = 14）, dimethyl sulfoxide post-treatment control group （DMSO group, n = 14）, and mdivi-1 post-treatment group （mdivi-1 group, n = 14）. Asphyxial CA was reproduced in animals, and they were resuscitated by CPR. In the mdivi-1 group or DMSO group, the animals were given mdivi-1 （ 1.2 mg/kg） or DMSO （0.1%） intravenously after restoration of spontaneous circulation （ ROSC ）. The neurological functions were assessed using neurological deficit score （NDS） determined at 24, 48 and 72 hours after CPR. The brain tissues were harvested at 72 hours after CPR. The histopathologic changes were assessed by hematoxylin and eosin （HE） staining, and the normal neuron was counted. The neuronal apoptosis was assessed with terminal dexynucleotidyl transferase-mediated dUTP nick end labeling （TUNEL） staining, and the expressions of cytochrome C （Cyt-C） protein in mitochondria and cytoplasm from hippocampus were determined by Western Blot. Results NDS in all experiment groups was gradually increased after CPR, and they were significantly lower than those of the sham group at 24, 48, and 72 hours （51.5±3.7 vs. 80.0±0.0, 59.3±3.6 vs. 80.0±0.0, 66.7 ± 2.6 vs. 80.0±0.0, all P 〈 0.05）. The number of normal pyramidal neurons in the hippocampal CA1 regionwas markedly reduced （cells/HP： 4.4 ± 1.1 vs. 23.1 ± 4.0, P 〈 0.05 ）, the apoptotic index was significantly increased [ （86.9 ±6.9）% vs. （3.4 ±0.8 ）%, P 〈 0.05 ], the expressions of Cyt-C in mitochondria were significantly decreased （A value： 0.46±0.18 vs. 1.00±0.00, P 〈 0.05）, and the expressions of Cyt-C in cytoplasm were significantly up-regulated （A value： 6.65 ± 0.21 vs. 1.00 ± 0.00,