Wang Hailian, Lu Shiduo, Yu Qiong, Liang Weimin, Gao Hui, Li Peiying, Gan Yu, Chen Jun, Gao Yanqin
State Key Laboratory of Medical Neurobiology, Department of Anesthesiology of Huashan Hospital, Fudan University, Shanghai, China.
Front Biosci (Elite Ed). 2011 Jan 1;3(2):604-15. doi: 10.2741/e273.
Neuroprotection afforded by volatile anesthetic preconditioning (APC) has been demonstrated in both in vivo and in vitro experiments, yet the underlying mechanism is poorly understood. We therefore investigated whether suppression of p38 MAPK, NF-kappa B and the downstream pro-inflammatory signaling cascade contribute to sevofurane APC-induced neuroprotection. Male Sprague-Dawley rats were exposed for 30 min/day on 4 consecutive days to ambient air or to sevoflurane (1.2% or 2.4%). Then rats were subjected to filament occlusion of the middle cerebral artery (MCAO) for 60 min, and euthanized 3 days after MCAO for measuring infarct volume. APC with sevofurane markedly improved neurological performance of stroke rats, significantly decreased infarct volume, and robustly suppressed activation of NF-kappa B and p38 MAPK, and expression of inflammatory cytokines. Furthermore, APC with sevofurane showed a direct inflammation-suppressing effect in rat brain receiving intracerebroventricular infusion of a dose of LPS that doesn't cause overt brain damage. Thus, the data suggest that APC with sevoflurane confers neuroprotection against focal ischemic brain injury, at least in part, by the anti-inflammatory effects of sevoflurane.
挥发性麻醉药预处理（APC）所提供的神经保护作用已在体内和体外实验中得到证实，但其潜在机制仍知之甚少。因此，我们研究了抑制p38丝裂原活化蛋白激酶（MAPK）、核因子κB（NF-κB）及下游促炎信号级联反应是否有助于七氟醚APC诱导的神经保护作用。将雄性Sprague-Dawley大鼠连续4天每天暴露于环境空气或七氟醚（1.2%或2.4%）中30分钟。然后对大鼠进行大脑中动脉（MCAO）丝线闭塞60分钟，并在MCAO后3天实施安乐死以测量梗死体积。七氟醚APC显著改善了中风大鼠的神经功能，显著减小了梗死体积，并有力地抑制了NF-κB和p38 MAPK的激活以及炎性细胞因子的表达。此外，七氟醚APC对接受脑室内注射一定剂量脂多糖（LPS）但未造成明显脑损伤的大鼠脑显示出直接的抗炎作用。因此，数据表明七氟醚APC至少部分通过七氟醚的抗炎作用对局灶性缺血性脑损伤起到神经保护作用。
