异丙酚预先给药对全脑缺血再灌注大鼠脑的保护作用  

Propofol protects against global cerebral Ischemla-reperfusion Injury In rats

作　　者：王彦松[1] 张联峰[1] 李继庆[1] 李志学[1] 姚红娟[1] 朱玉琦[1] 

机构地区：[1]哈尔滨医科大学第一附属医院麻醉科,150001

出　　处：《中华麻醉学杂志》2004年第8期596-599,共4页Chinese Journal of Anesthesiology

摘　　要：目的观察异丙酚预先给药对大鼠全脑缺血再灌注后细胞凋亡、脑源性神经营养因子(BDNF)及其受体酪氨酸激酶B(TrkB)mRNA表达的影响,在分子水平上探讨异丙酚对全脑缺血再灌注大鼠脑的保护作用及机制。方法 采用Pulsinelli-Brierley四动脉阻断法制备全脑缺血模型。雄性wistar大鼠57只,体重250-300 g,随机分为假手术组(SH组,n=15);缺血再灌注组(ISC组,n=21);异丙酚预处理组(PPC组,n=21),缺血前静脉注射异丙酚50 mg·kg-1后,用微量泵以1 mg·kg-1·min-1持续静注异丙酚2 h。每组按不同再灌注时间随机分为三个亚组:6 h、24 h、72 h亚组。缺血20 min后,于相应的再灌注时间点断头取脑,脑组织标本切片行HE染色,计数海马CA1区存活细胞数;原位末端标记(TUNEL)法检测凋亡细胞,计算凋亡指数;采用原位杂交技术测定BDNF及TrkB mRNA在海马CAl区表达的阳性率。结果HE染色光镜检查,PPC组海马CAl区锥体细胞核固缩、缺失等改变较ISC组明显减轻。(1)存活细胞数:各6h亚组差异无显著性;ISC及PPC组的24 h、72 h亚组低于SH组,ISC组又低于PPC组(P<0.05)。(2)凋亡细胞指数:ISC组及PPC组的6 h亚组低于24 h、72 h亚组。24 h亚组又低于72 h亚组(P<0.01);ISC组6 h、24 h、72 h亚组均高于SH、PPC组,PPC组6 h亚组与SH组差异无显著性,24Objective To investigate the effects of propofol pretreatment on apoptosis and the expression of mRNA for brain-derived neurotrophic factor (BDNF) and its receptor-tyrosine kinase B(TrkB) in hippocampus following global cerebral ischemia-reperfusion in rats.Methods Fifty-seven healthy male Wistar rats aged 2.5-3.5 months, weighing 250-300 g were randomly divided into 3 groups : (Ⅰ) sham operation group (SH, n=15); (Ⅱ) ischemia-reperfusion group (I/R, n=21) and (Ⅲ) propofol pretreatment group (PPC, n=21) . Group Ⅱ and Ⅲ were further divided into 3 subgroups according to the duration of reperfusion:6 h, 24 h and 72 h. Global cerebral ischemia was produced by permanent occlusion of bilateral vertebral arteries by cauterization and temporary occlusion of bilateral common carotid arteries and confirmed by loss of righting reflex, dilated pupils and EEG. The vascular clips on the carotid arteries were removed after 20 min ischemia interval. In group Ⅲ (PPC) the animals received a bolus of propofol 50 mg·kg-1 i.v. followed by intravenous propofol infusion at 1 mg·kg·min-1 for 2 h before I/R. At the end of 6 h, 24 h or 72 h reperfusion the animals were decapitated. The brains were immediately removed and sliced. The number of living neurons (HE Staining) and apoptotic neurons (TUNEL) in hippocampal CA1 were counted under light microscope. The expression of BDNF and TrkB mRNA in hippocampal CA1 were detected by in situ hybridization technique. Results The number of living neurons in hippocampal CA1 region was decreasing with increasing duration of perfusion in I/R group, from 181±19 /1.25 mm (6 h) to 103±23 /1.25 mm (24 h) and 51±18 /1.25 mm (72 h) ( P<0.01), while in PPC group most neurons in CA1 region were alive after 24 h and 72 h reperfusion. The numbers of apoptotic neurons in CA1 region were increasing as duration of reperfusion prolonged in I/R and PPC groups and were significantly less in PPC group than in I/R group at corresponding time points (P<0.01). The expression of BDNF and TrkB mRNA in C

关 键 词：异丙酚 SH BDNF 全脑缺血再灌注 mRNA表达 海马CA1区 大鼠 活细胞 雄性 受体酪氨酸激酶 

分 类 号：R96[医药卫生—药理学]