摘要
目的研究格列本脲对急性一氧化碳中毒大鼠的脑保护作用及其机制。方法40只成年、雄性sD大鼠按照随机数字表法分为A组对照组、B组模型组（CO）、C组二甲基亚砜组 （dimethyl sulfoxide, DMSO ）、D组格列本脲组（glibenclamide，BGC），每组10只。采用腹腔注射法（co150mL＆g）制作CO中毒模型，对照组给予等量空气腹腔注射。各组大鼠分别在实验开始后2h、6h、12h、24h经尾静脉采血，采用酶联免疫吸附测定法（nzymelinked immunosorbent assay, ELISA） 测定所有研究对象血清神经特异性烯醇化酶（neuronspecific enolase, NSE）及S-10013蛋白水平；造模后24h采用爬行法对大鼠神经功能缺损评估；评估后在麻醉状态下切取脑组织，对大鼠海马组织行尼氏染色。结果爬行法测试提示格列本脲治疗组平均神经功能缺损评分显著低于模型组和DMSO组（P〈0．01）；尼氏染色表明格列本脲对cO中毒后海马有明显的保护作用；格列本脲组血清NSE、S-100β蛋白明显低于模型组和DMSO组（P〈0．01）。结论格列本脲对急性CO中毒脑损伤有保护作用，其机制可能是通过抑制磺脲类受体1（sulfonylureareceptor1，Sur1）减轻脑细胞水肿、防止钙超载，从而起到减少脑细胞凋亡和坏死而发挥作用。
Objective To investigate the protective effect of Glibenclamide on brain injury in rats with acute carbon monoxide poisoning （ACMP）. Methods Forty SD rats were randomly divided into 4 groups： Group A： the air group, Group B： the CO group, Group C： the DMSO group, Group D： the Glibenclamide group. After the establishment of ACMP model （CO 150 ml/kg）, Group C was given equal amounts of saline and Dimethyl sulfoxide （DMSO） intraperitoneal injection at the same time point. Group D was given equal amounts of Glibenclamide intraperitoneal injection at the same time point. NSE, S-100B were measured by ELISA at 2h, 6h, 12h, 24h after injection respectively, then the neurological deficit scores of all rats were recorded. The rats were executed, and the brains were obtained for pathological staining. Results The levels of the neuronspecific enolase （NSE） and S-100B in serum of group B, C and D increased significantly compared to group A （P 〈0.01） at the times of 6h, 12h, 24h respectively. The NSE and S-100B levels in serum of group D decreased significantly （P 〈0.01） compared to group B and C. The neurological deficit scores of group D decreased significantly when compared to group B and C （P 〈0.01） at 24h. Cerebral pathomorphology damage was severe, but alleviated in treatment group. Conclusions Glibenclamide can reduce cerebral damage in rats with ACMP. Protective effect may be related to inhibiting sulfonylurea receptor 1 （SUR1）, controlling calcium overload and neuronal apoptosis.
作者
张致苍
杨慧平
李培杰
ZHANG Zhi-cang;YANG Hui-ping;LI Pei-jie
出处
《中国急救复苏与灾害医学杂志》
2018年第6期553-556,共4页
China Journal of Emergency Resuscitation and Disaster Medicine
关键词
急性CO中毒
格列本脲
Sur1
脑损伤
Acute carbon monoxide poisoning ACMP
Glibenclamide
Sulfonylurea receptor 1
Cerebal damage
