腺苷A1受体拮抗剂对异丙酚诱导脑缺血再灌注损伤大鼠细胞凋亡的影响  

Effect of adenosine A1 receptor antagonist on propofol induced apoptosis of cerebral cells in a rat model of focal cerebral ishemia reperfusion

作　　者：夏洪莲[1] 陈猛[1] 芦相玉[1] 胡春阳[1] 刘永梁[1] 张艳丽[1] 刘岩[1] 

机构地区：[1]黑龙江省牡丹江医学院红旗医院麻醉科

出　　处：《中国临床药理学与治疗学》2015年第7期727-731,共5页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家自然科学基金资助(81273926)

摘　　要：目的:观察异丙酚预处理对局灶性缺血再灌注损伤大鼠脑皮质半暗带区细胞凋亡及Bcl-2蛋白表达水平的影响,并探讨腺苷A1受体拮抗剂对异丙酚抗凋亡作用的影响。方法:通过阻塞大脑中动脉建立局灶性脑缺血再灌注模型(MCAO),异丙酚预处理采用经股静脉持续泵注30 min至缺血即刻。SD大鼠24只随机分为4组:假手术组(S组)、模型组(M组)、模型+异丙酚组(P组)、模型+异丙酚+腺苷A1受体拮抗剂组(D组)。拮抗剂组在异丙酚输注前30 min腹腔注射,1 mg/kg。再灌注24 h后,观察损伤后大脑皮质半暗带区组织形态学(HE染色)、Bcl-2蛋白表达量,凋亡细胞数(TUNEL法)。结果:P组与M组比较,神经元损害明显减轻;而D组与P组比较神经元明显出现核固缩或溶解,细胞水肿,差异具有统计学意义(P<0.01);P组BCL-2蛋白表达量高于M组(P<0.01),而D组BCL-2蛋白表达量明显较P组减少,差异具有统计学意义(P<0.01);P组凋亡细胞数明显少于M组(P<0.01),而D组与P组比较,凋亡细胞数明显增加,差异具有统计学意义(P<0.01)。结论:异丙酚预处理对局灶性脑缺血再灌注损伤大鼠脑皮质半暗带区细胞具有抗凋亡作用,机制可能与腺苷A1受体有关。AIM： To investigate the effect of propofol pretreatment on the expression of Bcl-2 and the rate of apoptosis in ischemia penumbra of cerebral cortex during focal cerebral ischemia-reperfusion in rat,and to explore adenosine A1 receptor antagonist on the influence of propofol antiapoptotic effect.METHODS： The rat model of cerebral ischemia reperfusion（ MCAO） was established by occluding middle cerebral artery. The rats were continuously injected with propofol for 30 min at a rate of 0. 1 m L·kg- 1·min- 1through the femoral vein until ischemia. The twenty-four Sprague-Dawley（ SD） rats were randomly divided into 4 groups： sham operation group（ group S）,MCAO group（ group M）,MCAO＋ propofol group（ group P）,MCAO ＋ propofol ＋DPCPX（ group D）. group D by intraperitoneal injection antagonist（ 1 mg / kg） before infusion propofol 30 min. After reperfusion 24 h,TUNEL staining and immunohistochemistry were used to detected the rate of apoptosis cell and the expression of Bcl-2.HE staining was used to evaluate the pathological morphological change of the brain slice. RESULTS：Compared with the group M,the damage of neurons in group P was obviously decreased; but when compared with group D,the neuron was significantly manifested as degeneration,necrosis and edema（ P〈0. 01）. The Bcl-2 protein observed in group P was significantly increased compared with group M（ P〈0. 01）. However,the expression of Bcl-2 protein was significantly reduced in group D（ P〈0. 01）. Less apoptosis cells were observed in group P compared with group M（ P〈0. 01）; but the apoptotic cells of group D were increased significantly（ P〈0. 05）. CONCLUSION： Propofol pretreatment 30 min obviously alleviated brain ischemia reperfusion injury rats cortex half dark stripe histomorphology,increase the Bcl-2 protein expression;decrease the rate of neuronal apoptosis,but application of adenosine A1 receptor antagonist（ DPCPX）,weaken the antiapoptotic effect,so that adenosine A1 receptors may be i

关 键 词：异丙酚 腺苷A1受体拮抗剂 脑缺血再灌注损伤 BCL-2 细胞凋亡 

分 类 号：R614[医药卫生—麻醉学]