依达拉奉缓解大鼠急性一氧化碳中毒所致脑损伤机制探讨  

Mechanisms of Edaravone in Alleviation of Brain Injury Induced by Acute Carbon Monoxide Poisoning in Rats

作　　者：刘磊[1,2] 蒋小建[3] 樊菲菲[1] 尹文[1] 王倩梅[1] 张宁[1] 庞芳宁[1] 

机构地区：[1]第四军医大学西京医院急救中心,西安710032 [2]新疆生产建设兵团医院急诊科,乌鲁木齐830000 [3]空军工程大学防空反导学院,陕西三原713800

出　　处：《解放军医药杂志》2016年第8期6-9,14,共5页Medical & Pharmaceutical Journal of Chinese People’s Liberation Army

基　　金：国家自然科学基金(8110413)

摘　　要：目的观察依达拉奉对大鼠急性一氧化碳(CO)中毒所致脑损伤的疗效,并探讨其可能的作用机制。方法取健康成年SD大鼠60只,随机分为生理盐水组(NS组)10只、CO中毒对照组(CO组)30只、CO中毒+依达拉奉实验组(实验组)20只。在实验第3、7、14 d后处死大鼠,用蛋白质印迹技术比较各时间点3组中髓鞘碱性蛋白质(myelin basic protein,MBP)的含量,以RT-PCR技术对3组中Bcl-2 mRNA和Bax mRNA的表达水平,以蛋白质印迹技术检测各时间3组Keap-1及Nrf-2的表达水平。结果实验3 d时3组MBP含量差异无统计学意义(P>0.05);在7、14 d时CO组和实验组较NS组明显下降(P<0.05),而实验组比CO组表达量增多(P<0.05);在3、7、14 d时CO组Bcl-2 mRNA表达水平均显著高于NS组(P<0.05),实验组显著高于NS组和CO组(P<0.05);CO组和实验组Bax mRNA表达水平在3、7、14 d均显著高于NS组(P<0.05),实验组Bax mRNA表达水平在3 d与CO组的表达差异无统计学意义(P<0.05),而在7、14 d显著低于CO组(P<0.05);在3、7、14 d时Keap1、Nrf-2含量CO组及实验组比NS组明显增多(P<0.01),实验组比CO组明显增多(P<0.01)。结论依达拉奉可减轻急性CO中毒所致的脑损伤程度,其作用机制可能是通过Keap-1/Nrf-2的途径而实现。Objective To observe effect of Edaravone in treatment of brain injury induced by acute carbon monoxide（ CO） poisoning and to investigate its possible mechanisms. Methods A total of 60 healthy adult SD rats were randomly divided into normal saline group（ NS group,n = 10）,CO positive control group（ CO group,n = 30） and CO ＋ Edaravone group（ n = 20）. The rats were sacrificed on 3rd,7thand 14 thd after treatment,and then in each group,contents of myelin basic protein（ MBP） at different time points were compared by Western blot method; expressions of Bcl-2 mRNA and Bax mRNA were compared by reverse transcription polymerase chain reaction（ RT-PCR） technology;expressions of Kelch-like ECH-associated protein-1（ keap-1） and NF-E2-related factor 2（ Nrf-2） were also compared by Western blot method. Results There were no significant differences in MBP content on 3rdd after treatment among three groups（ P〉 0. 05）. On 7th and 14thd after treatment,MBP contents in CO and CO ＋ Edaravone groups were significantly decreased compared with that in NS group（ P〈 0. 05）,and the contents in CO ＋ Edaravone group were higher than those in CO group（ P〈 0. 05）. On 3rd,7th and 14thd after treatment,expression levels of Bcl-2 mRNA in CO group were significantly higher than those in NS（ P〈 0. 05）,and the expression levels of Bcl-2 mRNA in CO ＋ Edaravone group were significantly higher than those in NS and CO groups（ P〈 0. 05）. Expression levels of Bax mRNA in CO group on 3rd,7th and 14thd after treatment were significantly higher than those in NS group（ P〈 0. 05）,and there was no significant difference in expression levels of Bax mRNA on 3^（rd）d after treatment between CO ＋ Edaravone group and NS group（ P 〉0. 05）; while the expression levels of Bax mRNA on 7^（th） and 14^（th） d after treatment in CO ＋ Edaravone group were significantly lower than those in CO group（ P〈 0. 05）. On 3^（rd）,7^（th） and 14 thd after treatment,Keap-1 and Nrf-

关 键 词：急性一氧化碳中毒 依达拉奉 细胞凋亡 氧化应激 髓鞘碱性蛋白 Keap1-Nrf2/ARE 大鼠 SD 

分 类 号：R827.176[医药卫生—临床医学] R971