亚甲蓝对兔心脏骤停后脑缺血再灌注损伤保护作用研究  

Protective effect of methylene blue on cerebral ischemia-reperfusion injury after cardiac arrest in rabbits

作　　者：苏成洋 任亮亮 梁志娟 司江华 于澄 SU Cheng-yang;REN Liang-liang;LIANG Zhi-juan;SI Jiang-hua;YU Cheng(Department of Neurology,The First People’s Hospital of Lanzhou,Lanzhou 730050,China)

机构地区：[1]兰州市第一人民医院神经内科,甘肃兰州730050

出　　处：《创伤与急危重病医学》2022年第5期319-323,共5页Trauma and Critical Care Medicine

摘　　要：目的研究亚甲蓝(MB)对兔心脏骤停后脑缺血再灌注损伤的保护作用,并探讨其用药剂量。方法选用50只健康清洁级家兔,随机分为假手术组、空白对照组、小剂量MB组(1.0 mg/kg)、中剂量MB组(5.0 mg/kg)及高剂量MB组(10.0 mg/kg)。采用体外电击致颤法建立心脏骤停心肺复苏(CPR)模型。在CPR开始即刻,空白对照组经腹腔注射生理盐水10 ml;小剂量MB组、中剂量MB组及高剂量MB组分别经腹腔注射MB注射液1.0 mg/kg、5.0 mg/kg及10.0 mg/kg。酶联免疫吸附法检测各组兔致颤前15 min及自主循环恢复(+ROSC)后1、6、12、24 h的脑损伤标志物神经元特异性烯醇化酶(NSE)、S-100β蛋白及凋亡蛋白酶半胱天冬酶-3(Caspase-3)水平。5组兔均于+ROSC后24 h处死,迅速取出全脑组织,采用干湿重法测定脑组织含水量,苏木精-伊红染色法观察海马CA1区病理变化。结果致颤前15 min,各组NSE、S-100β蛋白及Caspase-3比较,差异无统计学意义(P>0.05)。空白对照组、小剂量MB组、中剂量MB组及高剂量MB组+ROSC后1、6、12、24 h NSE、S-100β蛋白、Caspase-3以及+ROSC后24 h脑组织含水量均较假手术组明显增高,差异有统计学意义(P<0.05)。+ROSC后24 h,小剂量MB组、中剂量MB组及高剂量MB组脑组织含水量均低于空白对照组;小剂量MB组、中剂量MB组脑组织含水量低于高剂量MB组,且中剂量MB组低于小剂量MB组,差异均有统计学意义(P<0.05)。+ROSC后1、6、12、24 h,小剂量MB组、中剂量MB组及高剂量MB组NSE低于空白对照组;小剂量MB组、中剂量MB组NSE低于高剂量MB组,且中剂量MB组低于小剂量MB组,差异均有统计学意义(P<0.05)。+ROSC后1、6、12、24 h,空白对照组、高剂量MB组S-100β蛋白、Caspase-3比较,差异无统计学意义(P>0.05)。+ROSC后1、6、12、24 h,小剂量MB组、中剂量MB组S-100β蛋白、Caspase-3低于空白对照组,且中剂量MB组低于小剂量MB组,差异有统计学意义(P<0.05)。病理观察显示,Objective To investigate the protective effect of methylene blue(MB)on cerebral ischemia-reperfusion injury in rabbits,and to explore the optimal dose.Methods A total of 50 healthy clean rabbits were randomly divided into sham operation group,blank control group,low dose MB group(1.0 mg/kg),medium dose MB group(5.0 mg/kg)and high dose MB group(10.0 mg/kg).The cardiopulmonary resuscitation(CPR)model of cardiac arrest was established by external electric shock to cause ventricular fibrillation.Since the beginning of CPR,the blank control group was intraperitoneally injected with 10 ml normal saline,the low-,medium-,and high-dose MB groups were intraperitoneally injected with 1.0 mg/kg,5.0 mg/kg,and 10.0 mg/kg MB,respectively.The levels of brain injury markers neuron-specific enolase(NSE),S-100βprotein and apoptosis protease Caspase-3were detected by enzyme-linked immunosorbent assay at 15 minutes before fibrillation and 1,6,12 and 24 hours after return of spontaneous circulation(+ROSC).All rabbits in the 5 groups were sacrificed at 24 hours after+ROSC,and the whole brain tissue was quickly removed.The water content of brain tissue was determined by dry and wet weight method,and the pathological changes of hippocampal CA1 area were observed by hematoxylin and eosin staining.Results At 15 minutes before fibrillation,there were no significant differences in NSE,S-100βprotein and Caspase-3 between the five groups(P>0.05).The levels of NSE,S-100βprotein,Caspase-3 at 1,6,12 and 24 hours after+ROSC and water content of brain tissue at 24 hours after+ROSC in blank control group,low dose MB group,medium dose MB group,and high dose MB group were significantly higher than those in sham operation group(P<0.05).The water content of brain tissue at 24 hours after+ROSC in the low dose MB group,medium dose MB group and high dose MB group was significantly lower than that in the blank control group(P<0.05).The water content of brain tissue at 24 hours after+ROSC in the low dose MB group and the medium dose MB group was lower tha

关 键 词：兔 心脏骤停 脑缺血再灌注损伤 亚甲蓝 自主循环恢复 心肺复苏 

分 类 号：R459.7[医药卫生—急诊医学]