处理后而非处理前应用选择性β1-肾上腺素受体阻滞剂可以对短暂性前脑缺血的大鼠海马提供神经保护

背景β-肾上腺素受体阻滞剂对局灶性脑缺血有神经保护作用，但对于实验性全脑缺血的效应却不得而知。β-受体阻滞剂对缺血损伤后的易损脑组织是否有效应还未被检测。因此，我们通过大鼠研究了在缺血前或缺血后给予普萘洛尔（非选择性β-受体阻滞剂）、艾司洛尔和兰地洛尔（选择性β1-受体阻滞剂）对前脑缺血的神经保护作用。方法1．5％异氟炕麻醉，雄性SD大鼠双侧颈动脉阻断合并低血压（35mmHg）8分钟，在缺血前30分钟和后60分钟，静脉分别给予生理盐水10μl·h^-1、普萘洛尔100μg·kg^-1·min^-1、艾司洛尔200μg·kg^-1·min^-1或兰地洛尔50μg·kg^-1·min^-1。所有给药持续至再灌注后5天，此后所有的动物接受神经学和组织学评估。结果应用普萘洛尔、艾司洛尔或兰地洛尔对海马前脑缺血进行预处理不能提供神经保护。用普萘洛尔处理的大鼠运动能力评分更低，并且死亡率增加（达64％），但是与其他组之间没有明显的统计学差异。应用艾司洛尔、兰地洛尔而非普萘洛尔进行缺血后处理可以减少前脑缺血的神经损伤。然而，使用任何β-受体阻滞剂或生理盐水进行缺血后处理，各组大鼠之间的运动功能并没有差别。结论应用艾司洛尔、兰地洛尔进行缺血后处理可以对双侧颈动脉阻塞合并出血性休克大鼠的海马提供神经保护作用，而普萘洛尔却未显示有神经保护作用。在休克时使用β-受体阻滞剂可能非但不能产生神经保护作用，相反有可能会产生全身抑制而导致脑缺血加重。

BACKGROUND： β-Adrenoreceptor antagonists provide neuroprotection against focal cerebral ischemia, but the effects of these antagonists on experimental global cerebral ischemia are unknown. That is, the effect of β-adrenoreceptor antagonism in vulnerable brain regions after ischemic insult has not been examined. Therefore, we investigated the neuropro- tective effects of preischemic or postischemic administration of propranolol （a nonselective β-adrenoreceptor antagonist）, es- molol, and landiolol （selective β-adrenorecepmr 1 antagonists） against forebrain ischemia in rats. METHODS： IV adminis- tration of saline 10 μl· h^-1, propranolol 100 μg · kg^-1· min^-1, esmolo1200 μg · kg^-1 ·min ^-1, or landiolo150 μg · kg^-1· min ^-1 in male Sprague-Dawley rats was started 30 minutes before or 60 minutes after 8-minute bilateral carotid artery occlu- sion combined with hypotension （35 mm Hg） under isoflurane （1.5%） anesthesia. All drugs were administered continuously until 5 days after reperfusion, and the animals were evaluated neurologically and histologically after this 5-day period. RE- SULTS： Preischemic treatment with propranolol, esmolol, or landiolol failed to provide neuroprotection against forebrain is- chemia in the hippocampus. Rats treated with propranolol tended to have a worse score for motor activity and a higher mor- tality rate （up to 64% ）, but the differences with other groups were not statistically significant. Postisdmmic treannent with es- molol and landiolol, but not with propranolol, reduced neuronal injury after forebrain ischemia. However, motor activity did not differ among rats treated postischemically with any of the β-adrenoreceptor antagonists or saline. CONCLUSIONS： Postischemic treatment with esmolol and landiolol provided neuroprotection in the hippocampus in rats subjected to bilateral ca- rotid artery occlusion combined with hemorrhagic shod〈 whereas treatment with propranolol failed to show neuroprotection. We suggest that concomitant β-bloade and shod〈 might work as a systemic depressant, rather than a neuroprotectant, resul- ting in exacerbation of cerebral ischemia.