β2肾上腺素能受体缺乏小鼠缺血性脑损伤被削弱  

作　　者：翁梅琳(译) 杜冬萍(校) 

出　　处：《麻醉与镇痛》2012年第6期1-8,共8页Anesthesia & Analgesia

摘　　要：背景一些β肾上腺素能受体（β-adrenergic receptor，βAR）拮抗剂具有针对脑缺血的神经保护作用。然而，研究发现β2肾上腺素能受体激动剂克仑特罗可增强神经生长因子表达、起到神经保护的作用。我们使用β2肾上腺素能受体敲除小鼠和一种选择性的β2受体拮抗剂，来测试β2肾上腺素能受体缺失对短暂性局灶性脑缺血预后的影响。方法以线栓法大脑中动脉阻闭（middle cerebral artery occlusion，MCAO）60分钟后再灌注24小时。再灌注24小时进行神经系统评分，梗死范围用甲酚紫或2，3，5－氯化三苯基四氮唑染色进行测定。我们使用敲除β2肾上腺素能受体的小鼠和野生型同类系的小鼠进行研究。野生型的小鼠分为两组，分别在行MCAO前30分钟给予腹腔注射普萘洛尔118551（0．2mg／kg）或0．9％生理盐水（每组10只）。以免疫组化和Westernblot检测缺血后Hsp72表达的变化。结果和野生型同窝出生的小鼠相比，β2肾上腺素能受体敲除小鼠在大脑中动脉阻闭60分钟、再灌注24小时后，大脑梗死体积减少了22．3％（39．7±10．7mm2vs51．0±11．4mm3，n=10，P=0．034）。同时，用选择性β2肾上腺素能受体拮抗剂普萘洛尔118551预处理的小鼠和注射生理盐水的小鼠相比，其大脑的梗死体积也显著降低（32．8±11．9mm3vs43．8±10．3mm3，n=10，P=0．041）。β2肾上腺素能受体敲除的小鼠和接受普萘洛尔118551预处理的小鼠神经系统评分显著增加。β2肾上腺素能受体敲除小鼠脑缺血后，Hsp72整体水平和免疫阳性细胞的数量都明显增加。结论在β2肾上腺素能受体敲除小鼠和用选择性β2肾上腺素能受体拮抗剂预处理的小鼠中，大脑中动脉阻闭后脑损伤减轻了，神经功能得到改善。这和脑缺血时陡肾上腺素能受体激活会使促存活信号转化为促死亡信号的说法是一致的。神经系统的保护作用和Hsp72的�BACKGROUND： Several β-adrenergic receptor （BAR） antagonists have been shown to have neuroprotective effects against cerebral ischemia. However, denbuterol, a β2AR agonist, was shown to have neuroprotective activity by increasing nervegrowth factor expression. We used β2AR knockout mice and a β2 selective antagonist to test the effect of loss of β2ARs on outcome from transient focal cerebral ischemia. METHODS： Ischemia was induced by the intraluminal suture method, for 60 min of middle cerebral artery occlusion （MCAO） followed by 24 h reperfusion. Neurological score was determined at 24 h reperfusion and infarct size was determined by cresyl violet or 2, 3, 5-triphenyltetrazolium chloride staining. β2AR knockout mice and wild-type congenic FVB/N controls were studied, as well as 2 groups of wild type mice given either ICI 118, 551 （0.2 mg/kg） or 0.9% saline intraperitoneally 30 rain before MCAO （n = 10 per group）. Changes in expression of heat shirk protein （Hsp） 72 after ischemia were examined by immunohistochemistry and western blots. RESULTS： Compared with wild type littermates, infarct volume was decreased by 22.3% in β2AR knockout mice （39.7 ± 10.7 mm3 vs 51.0 ± 11.4 mm3, n = 10/group, P = 0.034） after 60 min of MCAO followed by 24 h reperfusion. Pretreatment with a β2AR selective antagonist, ICI 118, 551, also decreased infarct size significantly, by 25.1%, compared with the saline control （32.8 ± 11.9 mm3 vs 43.8 ± 10.3 mm3, n = 10/group, P = 0. 041 ）. Neurological scores were also significantly improved in mice lacking the I32AR or pretreated with ICI 118, 551. After cerebral ischemia, total levels of Hsp72 and the number of Hsp72 immunopositive cells were greater in micelacking β2 AR. CONCLUSIONS： Brain injury is reduced and neurological outcome improved after MCAO in mice lacking the β2AR, or in wild type mice pretreated with aselective β2AR antagonist. This is consistent with a shift away from prosurvival signaling to prodeath signaling in the presence

关 键 词：Β2肾上腺素能受体激动剂 缺血性脑损伤 肾上腺素能受体拮抗剂 小鼠 短暂性局灶性脑缺血 Westernblot 氯化三苯基四氮唑染色 注射生理盐水 

分 类 号：R562.25[医药卫生—呼吸系统]