慢性摄入尼古丁加重大鼠脑缺血再灌注损伤性脑水肿的初步研究  

Preliminary study on the effect of chronic nicotine intake on cerebral edema induced by ischemic reperfusion in rats

作　　者：陈晓[1] 赵津京[2] 蒋功达[1] 徐烈钧[1] 段喜森[1] 佘志峰[1] 陈炜炜[1] 潘树义[3] 

机构地区：[1]解放军第一一三医院高压氧科,浙江省宁波315040 [2]南方医科大学附属解放军第三○五医院 [3]海军总医院全军高压氧中心

出　　处：《中华航海医学与高气压医学杂志》2014年第3期190-193,共4页Chinese Journal of Nautical Medicine and Hyperbaric Medicine

摘　　要：目的 观察尼古丁慢性摄入加重大鼠脑缺血再灌注损伤性脑水肿的程度,并初步探讨其作用机制.方法 10周龄雄性Sprague Dawley（SD）大鼠90只,按数字表法随机分为对照组（45只）和尼古丁组（45只）,分别给予生理盐水[0.5 ml/（kg·d）]、尼古丁[3 mg/（kg·d）]皮下注射,1次/d.6周后将2组大鼠制作成大脑中动脉缺血再灌注损伤模型,分5个时间点（每组每个时间点9只）观察脑水肿的发生情况和程度.取对照组和尼古丁组脑微血管内皮细胞株bEnd.3进行培养,分为3组：对照组、尼古丁组（1μmol/L）、尼古丁＋α-金环蛇毒素组（尼古丁1 μmol/L,α-金环蛇毒素0.1μmol/L）,检测3组细胞通透性的变化及细胞中水通道蛋白1（aquaporin 1,AQP1）的表达变化.结果 与对照组比较,尼古丁组再灌注3.0h后脑水肿的程度明显加重,再灌注12.0 h时脑组织含水量最大[2组分别为（86.53±2.26）％和（90.47±1.94）％],差异有统计学意义（P＜0.01）.对脑微血管内皮细胞株bEnd.3的检测发现,尼古丁组细胞通透性[（143±11）％]明显高于对照组[（100±13）％],差异有统计学意义（P＜0.01）;尼古丁＋α-金环蛇毒素组通透性[（114±15）％]较尼古丁组明显改善,差异有统计学意义（P＜0.05）.细胞内AQP1蛋白的表达,尼古丁组（1.49±0.19）明显高于对照组（1.04±0.12）,差异有统计学意义（P＜0.01）;尼古丁＋α-金环蛇毒素组通透性（1.20 ±0.14）较尼古丁组有所减少,差异有统计学意义（P＜0.05）.结论 在尼古丁刺激下,脑微血管内皮细胞通透性的增加是脑水肿加重的原因.内皮细胞中α7尼古丁乙酰胆碱受体（α7nAchR）和AQP1蛋白参与了其中的发生过程.Objective To observe the effect of chronic nicotine intake on cerebral edema induced by ischemic reperfusion in rats and also to investigate the mechanism involved.Methods Ninety male SD rats,with an age of 10 weeks,were randomly divided into the normal saline group （n =45）,and the nicotine group （n =45）.The animals in the 2 groups were respectively given physiological saline （0.5 ml/kg · d） and nicotine （subcutaneous injection with nicotine at a dosage of 3mg/kg · d） for 6 weeks.After 6 weeks,models of cerebral injury induced by ischemic reperfusion were developed,and occurrence and seriousness of cerebral edema were observed at 5 different time points （there were 9 animals in each group at each different time point）.Endothelial cell strains from cerebral micro vessels,bEnd.3,were collected for culture from the animals of the control group and the nicotine group.The animals in the nicotine group were further divided into zthe nicotine group （1μmol/L） and the nicotine ＋ α-bungarotoxin group （nicotine 1 μmol/L,α-bungarotoxin 0.1μmol/L）.Changes in cell permeability and the expressions of aquaporin 1 （AQP1） were detected in the animals of the 3 groups.Results Three hours after ischemic reperfusion,cerebral edema in the animals of the nicotine group obviously worsened,as compared with that of the animals in the control group.Cerebral water contents of the 2 groups came to peak levels at 12.0 h after ischemic reperfusion,reaching the levels of（86.53 ± 2.26） % and（90.47 ± 1.94） % respectively,with statistical significance （P 〈 0.01）.Detection of bEnd.3 in the cerebral micro-vessel endothelial cell strains revealed that cell permeability in the nicotine group [（114 ± 15）%] was significantly higher than that of the control group [（100 ± 13）%],with statistical significance （P 〈0.01）.Cell permeability in the nicotine ＋ α-bungarotoxin group significantly improved,as compared with that of the nicotine group,also with statistical significance（P 〈

关 键 词：尼古丁 内皮细胞通透性 水通道蛋白1 α7尼古丁乙酰胆碱受体 α-金环蛇毒素 

分 类 号：R743.3[医药卫生—神经病学与精神病学]