大麻素Ⅰ型受体参与异氟醚预处理诱导的大鼠脑缺血耐受

Cannabiniod Receptor 1 Involved in the Ischemic Tolerance Induced by Isoflurane Preconditioning in Rats

目的:探讨大麻素Ⅰ型受体(CB1受体)是否参与异氟醚预处理诱导的大鼠脑缺血耐受。方法:48只雄性SD大鼠随机分为6组(n=8):假手术组SHAM:仅暴露颈总动脉,不结扎血管;对照组MCAO:阻塞大鼠大脑中动脉2 h;异氟醚预处理组ISO:大鼠吸入异氟醚(1.5%)1 h/d,连续5 d;溶剂+异氟醚预处理组(Vehicle+ISO)和CB1受体拮抗剂+异氟醚预处理组(AM251+ISO):每日在吸入异氟醚前30 min分别给予溶剂(二甲基亚砜:Tween-80:生理盐水=1:1:18)3 mL/kg(ip)和AM251(i.p.),连续5 d;CB1受体拮抗剂组(AM251):每日腹腔注射(i.p.)AM251)1 mg/kg,连续5 d。除SHAM组外其余各组均在最后一次预处理24 h后行颈内动脉线栓法致大脑中动脉栓塞(2 h)模型,观察再灌注后24 h神经行为学评分,然后取大脑行2,3,5-氯化三苯四唑(TTC)染色以计算脑梗死容积百分比。结果:SHAM组神经行为学正常且未见梗死灶;ISO组和Vehicle+ISO组脑梗死体积百分比分别(29.3±4.2%)和(31.5±3.4)%,明显小于MCAO组、AM251组和AM251+ISO组(P<0.05);神经行为学评分ISO组(12.1±0.6)和Vehicle+ISO组(11.1±0.8)明显高于MCAO组(7.4±1.2)、AM251组(7.6±1.1)和AM251+ISO组(8.6±1.2)(P<0.05);而AM251组、AM251+ISO组与MCAO组之间神经行为学评分和脑梗死体积百分比均无统计学意义。结论:CB1受体可能参与了异氟醚预处理诱导的大鼠脑缺血耐受。

Objective： To investigate whether cannabinoid receptor 1（CB1） participates in the ischemic tolerance induced by isoflurance preconditioning in rats.Methods： Forty-eight male SD rats were randomly assigned to 6 groups（n=8 in each group）： Sham group only received sham operation,control（Con） group underwent ischemic for 2 h and reperfusion for 24 h,isoflurane（ISO） group inhaled isoflurane（1.5%） for 1 h a day for 5 consecutive days,vehicle plus isoflurane（Vehicle＋ISO） group and AM251 plus isoflurane（AM251＋ISO） group inhaled isoflurance for 1 h,and were respectively injected with vehicle（DMSO：Tween-80：sale = 1：1：18） 3 mL/kg and AM251 1 mg/kg（i.p.） 30 min prior to the onset of isoflurance preconditioning once a day for 5 consecutive days,AM251 group received AM251（i.p.） once a day for 5 consecutive days.Twenty-four hours after last treatment,all groups except sham group received the middle cerebral artery occlusion（120 min）.The neurobehavioral score of all rats were evaluated at 24 h after reperfusion.The infarct volume,as a percentage of volume at normal cerebral hemisphere,was then assessed by 2,3,5 triphenyltetrazolium chloride（TTC） staining after the evaluation of neurobehavioral score.Results： In sham group,no neurological deficits and infarct volume were observed.The infarct volume percentage in ISO group and Vehicle＋ISO group was respectively（29.3 ±4.2）% and（31.5 ±3.4）%,which was significantly smaller than that in MCAO group,AM251 group and AM251＋ISO group（P0.05）.The neurobehavioral score in ISO group（12.1±0.6） and Vehicle＋ISO group（11.1±0.8） were significantly higher than that in MCAO group（7.4±1.2）,AM251group（7.6±1.1）,and AM251＋ISO（8.6±1.2） group（P0.05）.No significant difference was observed between AM251 group,AM251＋ISO group and MCAO group.Conclusion： The ischemic tolerance induced by isoflurane preconditioning in rats may participate in the activation of the CB1 receptor in the brain.