异氟烷预处理可诱导新生大鼠产生依赖于诱导型一氧化氮合酶的神经保护作用。
Isoflurane preconditioning induces neuroprotection that is inducible nitric oxide synthase-dependent in neonatal rats.
作者信息
Zhao Ping, Zuo Zhiyi
机构信息
Department of Anesthesiology, University of Virginia Health System, Charlottesville, Virginia 22908-0710, USA.
出版信息
Anesthesiology. 2004 Sep;101(3):695-703. doi: 10.1097/00000542-200409000-00018.
BACKGROUND
Perinatal stroke is a common human disease. Neonatal brains are immature and engaged in active synaptogenesis. Preconditioning adult rats with the volatile anesthetic isoflurane induces neuroprotection. Whether isoflurane preconditioning induces neuroprotection in neonates is not known.
METHODS
Seven-day-old Sprague-Dawley rats had left common carotid arterial ligation followed by hypoxia with 8% oxygen for 1, 2, or 2.5 h at 37 degrees C. Isoflurane preconditioning with 1 or 1.5% isoflurane for 30 min was performed at 24 h before the brain hypoxia/ischemia. The inducible nitric oxide synthase inhibitor aminoguanidine (200 mg/kg, intraperitoneally) was administered 30 min before the isoflurane pretreatment. The weight ratio of left to right cerebral hemispheres at 7 days after the brain hypoxia/ischemia was calculated. The mortality during the period from cerebral hypoxia/ischemia to 7 days afterwards was monitored. In another experiment, 6-day-old rats were exposed to 1.5% isoflurane for 30 min. The cerebral hemispheres were removed at various time points for Western analysis of inducible nitric oxide synthase.
RESULTS
The mortality was about 40% in neonates with brain hypoxia/ischemia for 2 h or 2.5 h and was not altered by isoflurane preconditioning. The weight ratio of left/right cerebral hemispheres in the survivors was 0.99 +/- 0.02, 0.65 +/- 0.19, and 0.86 +/- 0.15 (n = 7-18) for the rats in control, brain hypoxia/ischemia for 2.5 h, and isoflurane preconditioning plus brain hypoxia/ischemia for 2.5 h groups, respectively (P < 0.05 for the comparisons between control versus brain hypoxia/ischemia and brain hypoxia/ischemia versus isoflurane preconditioning plus brain hypoxia/ischemia). This isoflurane preconditioning-induced neuroprotection was abolished by aminoguanidine (the weight ratio was 0.61 +/- 0.18, n = 12). Isoflurane induced a time-dependent increase in the inducible nitric oxide synthase proteins.
CONCLUSIONS
Isoflurane preconditioning induces neuroprotection in neonatal rats. This neuroprotection is inducible nitric oxide synthase-dependent.
背景
围产期卒中是一种常见的人类疾病。新生大鼠的大脑尚未发育成熟，且处于活跃的突触形成阶段。用挥发性麻醉剂异氟烷预处理成年大鼠可诱导神经保护作用。而异氟烷预处理是否能诱导新生大鼠产生神经保护作用尚不清楚。
方法
对7日龄的Sprague-Dawley大鼠进行左侧颈总动脉结扎，然后在37℃下用8%氧气进行1、2或2.5小时的缺氧处理。在脑缺氧/缺血前24小时，用1%或1.5%的异氟烷预处理30分钟。在异氟烷预处理前30分钟腹腔注射诱导型一氧化氮合酶抑制剂氨基胍（200mg/kg）。计算脑缺氧/缺血后7天左侧与右侧大脑半球的重量比。监测从脑缺氧/缺血到之后7天期间的死亡率。在另一项实验中，对6日龄大鼠暴露于1.5%异氟烷30分钟。在不同时间点取出大脑半球进行诱导型一氧化氮合酶的蛋白质印迹分析。
结果
脑缺氧/缺血2小时或2.5小时的新生大鼠死亡率约为40%，异氟烷预处理未改变该死亡率。对照组、脑缺氧/缺血2.5小时组以及异氟烷预处理加脑缺氧/缺血2.5小时组大鼠存活者的左右大脑半球重量比分别为0.99±0.02、0.65±0.19和0.86±0.15（n = 7 - 18）（对照组与脑缺氧/缺血组以及脑缺氧/缺血组与异氟烷预处理加脑缺氧/缺血组之间比较，P < 0.05）。氨基胍消除了异氟烷预处理诱导的神经保护作用（重量比为0.61±0.18，n = 12）。异氟烷诱导诱导型一氧化氮合酶蛋白呈时间依赖性增加。
结论
异氟烷预处理可诱导新生大鼠产生神经保护作用。这种神经保护作用依赖于诱导型一氧化氮合酶。
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