CAJ | 학술논문

目的评价异丙酚后处理对大鼠脑缺血再灌注损伤的影响:长期观察.方法健康雄性SD大鼠144只,体重250～280g,7～8周龄,采用随机数字表法,将其随机分为4组(n=36):假手术组(S组)、缺血再灌注组(I/R组)、异丙酚后处理组(P组)和溶媒对照组(I组).I/R组、P组和I组采用线栓法阻塞大脑中动脉60min进行再灌注的方法制备局灶性脑缺血再灌注损伤模型.P组在再灌注即刻开始静脉输注异丙酚20 mg·kg-1·h-1 2h,S组和I/R组给予等容量生理盐水,I组给予等容量10％脂肪乳.4组分别于术后1、14、28d取5只大鼠,进行神经功能评分及脑梗死体积测定；4组各取6只大鼠,分别于术后9、23d开始进行Morris水迷宫测试,连续6 d;4组分别于术后1、14、28 d取5只大鼠,取海马组织,测定使君子酸( AMPA)受体GluR1亚基及其在胞膜上表达水平,计算二者比值(胞膜GluR1亚基/GluR1亚基).结果与S组比较,I/R组神经功能评分和跨越平台次数降低,脑梗死体积增加,逃避潜伏期延长,胞膜GluR1亚基/GluR1亚基增加(P＜0.05),而海马组织GluR1亚基表达差异无统计学意义(P＞0.05)；异丙酚后处理可抑制脑缺血再灌注诱导的上述改变(P＜0.05).结论异丙酚后处理减轻大鼠脑缺血再灌注损伤的效应可连续到术后28d,其部分机制与抑制含GluR1亚基AMPA受体向细胞膜转运有关.
목적 평개이병분후처리대대서뇌결혈재관주손상적영향:장기관찰.방법 건강웅성SD대서144지,체중250～280g,7～8주령,채용수궤수자표법,장기수궤분위4조(n=36):가수술조(S조)、결혈재관주조(I/R조)、이병분후처리조(P조)화용매대조조(I조).I/R조、P조화I조 채용선전법조새대뇌중동맥60min진행재관주적방법제비국조성뇌결혈재관주손상모형.P조재재관주즉각개시정맥수주이병분20 mg·kg-1·h-1 2h,S조화I/R조급여등용량생리염수,I조급여등용량10％지방유.4조분별우술후1、14、28d취5지대서,진행신경공능평분급뇌경사체적측정；4조각취6지대서,분별우술후9、23d개시진행Morris수미궁측시,련속6 d;4조분별우술후1、14、28 d취5지대서,취해마조직,측정사군자산( AMPA)수체GluR1아기급기재포막상표체수평,계산이자비치(포막GluR1아기/GluR1아기).결과 여S조비교,I/R조신경공능평분화과월평태차수강저,뇌경사체적증가,도피잠복기연장,포막GluR1아기/GluR1아기증가(P＜0.05),이해마조직GluR1아기표체차이무통계학의의(P＞0.05)；이병분후처리가억제뇌결혈재관주유도적상술개변(P＜0.05).결론 이병분후처리감경대서뇌결혈재관주손상적효응가련속도술후28d,기부분궤제여억제함GluR1아기AMPA수체향세포막전운유관.
Objective To investigate the long-term effects of propofol postconditioning on cerebral ischemia-reperfusion (I/R) injury in rats.Methods One hundred and forty-four healthy male SD rats,aged 7-8 weeks,weighing 250-280 g,were equally and randomly divided into 4 groups:sham operation group (group S),I/R group,propofol postconditioning group (group P) and intralipid group (group I).The animals were anesthetized with intraperitoneal 10％ chloral hydrate 300 mg/kg.Focal cerebral ischemia was induced by occlusion of middle cerebral artery for 60 min using a nylon thread with a rounded tip which was inserted into internal carotid artery in groups I/R,P and I.Two hour infusion of propofol was started at 20 mg· kg- 1· h- 1 immediately after the onset of reperfusion in group P,while the equal volume of normal saline was given instead in S and I/R groups,and 10％ intralipid was given instead in group I.Five rats in each group were chosen on day 1,14 and 28 after operation for assessment of neurological behavior and detection of cerebral infarct volume.Six rats in each group were chosen to perform Morris water maze test at day 9 and 23 after operation for 6 consecutive days.Five rats in each group were sacrificed on day 1,14 and 28 after operation and the hippocampal tissues were isolated for determination of the expression of GluR1-containing AMPA (GluR1-AMPA) receptor and GluR1-AMPA receptor in cell membrane.The ratio of GluR1-AMPA receptor in cell membrane/GluR1-AMPA receptor was calculated.Results Compared with group S,neurological behavior scores and the number of animals' swimming across the platform were significantly decreased,cerebral infarct volume was significantly enlarged,escape latency was significantly prolonged,and ratio of GluR1-AMPA receptor in cell membrane/GluR1-AMPA receptor was significantly increased ( P ＜ 0.05),while no significant change in the expression of GluR1-AMPA receptor was found in I/R group ( P ＞0.05).Propofol postconditioning inhibited cerebral I/R-induced changes mentioned above ( P ＜ 0.05).Conclusion The brain protection against focal I/R injury by propofol postconditioning can last for 28 days after operation and the inhibition of trafficking of GluR1-AMPA receptor from cytoplasm to cell membrane may contribute to this long-term brain protection.