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目的:评价线粒体通透性转换孔(mPTP)在右美托咪定减轻大鼠脑缺血再灌注损伤中的作用。方法:清洁级健康成年雄性SD大鼠80只，体重250～300 g，采用随机数字表法分为5组(n n＝16)：假手术组(S组)仅分离右侧颈总动脉，不阻塞；脑缺血再灌注组(I/R组)采用线栓法阻塞右侧颈总动脉2 h恢复灌注的方法制备大鼠局灶性脑缺血再灌注损伤模型；右美托咪定组(D组)脑缺血前和再灌注即刻分别腹腔注射右美托咪定50 μg/kg；mPTP开放剂苍术苷组(A组)脑缺血前10 min时侧脑室注射2 mmol/L苍术苷15 μl，余操作同I/R组；苍术苷＋右美托咪定组(A＋D组)脑缺血前10 min时侧脑室注射2 mmol/L苍术苷15 μl，余操作同D组。于再灌注24 h时行神经功能缺陷评分(NDS)后，处死大鼠取脑组织，提取线粒体，分别测定脑梗死体积、谷胱甘肽过氧化物酶(GSH-Px)和MDA含量、线粒体ATP酶(ATPase)活性、线粒体膜电位(MMP)、Bcl-2和Bax蛋白表达、mPTP开放程度。n 结果:与S组比较，其余各组大鼠NDS、脑梗死体积百分比和MDA含量升高，Bax蛋白表达上调，mPTP开放程度增加，GSH-Px含量、MMP、Nan ＋-Kn ＋-ATPase和Can 2＋-Mgn 2 ＋-ATPase活性降低，Bcl-2蛋白表达下调(n P<0.05)；与I/R组比较，D组大鼠NDS、脑梗死体积百分比和MDA含量降低，Bax蛋白表达下调，mPTP开放程度减少，GSH-Px含量、MMP、Nan ＋-Kn ＋-ATPase和Can 2＋-Mgn 2 ＋-ATPase活性升高，Bcl-2蛋白表达上调(n P<0.05)；与D组比较，A＋D组大鼠NDS、脑梗死体积百分比和MDA含量升高，Bax蛋白表达上调，mPTP开放程度增加，GSH-Px含量、MMP、Nan ＋-Kn ＋-ATPase和Can 2＋-Mgn 2 ＋-ATPase活性降低，Bcl-2蛋白表达下调(n P<0.05)。n 结论:mPTP参与了右美托咪定减轻大鼠脑缺血再灌注损伤的过程。“,”Objective:To evaluate the role of mitochondrial permeability transition pore (mPTP) in attenuation of cerebral ischemia-reperfusion (I/R) injury by dexmedetomidine in rats.Methods:Eighty clean-grade healthy male Sprague-Dawley rats, weighing 250-300 g, were assigned into 5 groups (n n=16 each) using a random number table method: sham operation group (group S), group I/R, dexmedetomidine group (group D), atractyloside (a specific opener of mPTP) group (group A), and atractyloside plus dexmedetomidine group (group A+ D). The focal cerebral I/R was produced by 2-h right middle cerebral artery occlusion followed by 24-h reperfusion. Dexmedetomidine (50 μg/kg) was intraperitoneally injected before ischemia and immediately after onset of reperfusion in group D. Atractyloside (2 mmol/L, 15 μl) was injected into the lateral ventricle at 10 min before ischemia, and the other treatments were similar to those previously described in group I/R. In group A+ D, atractyloside (2 mmol/L, 15 μl) was injected into the lateral ventricle at 10 min before ischemia, and the other treatments were similar to those previously described in group D. The neurological deficit score (NDS) was assessed at 24 h of reperfusion. The rats were then sacrificed, brain tissues were obtained, and mitochondria were extracted for determination of the cerebral infarct size, contents of glutathione peroxidase (GSH-Px) and MDA, mitochondrial ATPase (ATPase) activity, mitochondrial membrane potential (MMP) and expression of Bcl-2 and Bax protein and opening of mPTP.n Results:Compared with group S, the NDS, percentage of cerebral infarct size, and MDA content were significantly increased, the expression Bax protein was up-regulated, opening of mPTP was increased, the GSH-Px content, MMP and activities of Nan + -Kn + -ATPase and Can 2+ -Mgn 2 + -ATPase were decreased, and the expression of Bcl-2 protein was down-regulated in the other groups (n P<0.05). Compared with group I/R, the NDS, percentage of cerebral infarct size, and MDA content were significantly decreased, the expression Bax protein was down-regulated, opening of mPTP was decreased, the GSH-Px content, MMP and activities of Nan + -Kn + -ATPase and Can 2+ -Mgn 2 + -ATPase were increased, and the expression of Bcl-2 protein was up-regulated in group D (n P<0.05). Compared with group D, the NDS, percentage of cerebral infarct size, and MDA content were significantly increased, the expression Bax protein was up-regulated, opening of mPTP was increased, the GSH-Px content, MMP and activities of Nan + -Kn + -ATPase and Can 2+ -Mgn 2 + -ATPase were decreased, and the expression of Bcl-2 protein was down-regulated in group A+ D (n P<0.05).n Conclusion:mPTP is involved in reduction of I/R-induced cerebral I/R injury by dexmedetomidine in rats.