咪达唑仑对新生猪缺氧缺血性脑损伤的影响

Effects of midazolam on hypoxic-ischemic brain injury in neonatal piglets

目的评价咪达唑仑对新生猪缺氧缺血性脑损伤的影响。方法雄性新生猪24头，日龄3～7d，体重1．8～3．0kg，随机分为3组（n=8）：假手术组（S组）、缺氧缺血性脑损伤＋盐水组（HI-S组）和缺氧缺血性脑损伤＋咪达唑仑组（HI-M组）。HI-S组和HI-M组采用窒息性心跳骤停后心肺复苏的方法制备缺氧缺血性脑损伤模型。自主循环恢复（ROSC）后3h，各组均静脉输注芬太尼10—30μg·kg-1·h-1和泮库溴铵0．1-0．2mg·kg-1·h-1，HI-M组同时静脉输注咪达唑仑0．05mg·ks～·h。至ROSC后24h，HI-S组和s组静脉输注等容量生理盐水。于模型制备前（基础状态）、低氧37min、吸入空气5min、窒息5min、ROSC后6、12和24h时取动脉血样行血气分析，并记录各时点MAP；于ROSC后48、72、96及240h时行神经行为学评分（NBS），于ROSC后240h时取脑组织，计数纹状体（壳状核和尾状核）存活神经元，计算存活神经元密度。结果与S组和基础值比较，HI—S组和HI—M组低氧窒息期间动脉血氧分压降低，窒息5min时动脉血二氧化碳分压升高，pH值和MAP降低（P〈0．05），HI-M组和HI-S组各时点上述指标比较差异无统计学意义（P〉0．05）。与S组比较，HI-S组和HI-M组壳状核和尾状核存活神经元密度降低（P〈0．01），ROSC后48～96h时NBS评分升高（P〈0．05）；与HI-S组比较，HI-M组壳状核和尾状核存活神经元密度明显增加，Rosc后72和96h时NBS评分降低（P〈0．05）。结论心肺复苏早期应用咪达唑仑可减轻新生猪缺氧缺血性脑损伤。

Objective To investigate the effects of midazolam on hypoxic-ischemic （HI） brain injury in neonatal piglets. Methods Twenty-four newborn male piglets 3-7 days old weighing 1.8-3.0 kg wererandomly divided into 3 groups （n = 8 each） ： sham group （group S）, HI ＋ normal saline group （group HI-S） and HI ＋ midazolam group （group HI-M）. The animals of group HI-S and HI-M were subjected to 7 rain of hypoxia, producing asphyxic cardiac arrest, followed by cardiopulmonary resuscitation. At 3 h after restoration of spontaneous circulation （ROSC）, animals received i.v. infusion of fentanyl at a rate of 10-30μg·kg-1·h-1 and pancumnium at a rate of 0.1-0.2 mg· kg-1 . h-1 from 3 h after ROSC to 24 h after ROSC to maintain the anesthesia. In addition, midazolam at a rate of 0.05 mg· kg-1· h- 1 was infused simultaneously Until 24 h after ROSC in HI-M group, while the equal volume of normal saline was infused instead in group HI-S and S. Arterial blood samples were taken before hypoxia （baseline）, and at 37 rain of hypoxia, 5 min of air inspiration, 5 rain of asphyxia and 6, 12, and 24 h after ROSC for blood gas analysis, and MAP was monitored at the each time point. Neurological behavior was assessed and scored （NBS） at 48, 72, 96 and 240 h after ROSC. Brains were removed at 10 h after ROSC, the remaining viable neurons in putamen and caudate nucleus were counted and the density of viable neurons was determined using light microscopic examination. Results PaO2 was significantly decreased during hypoxia-asphyxia, and PaCO2 was significantly increased, while pH value and MAP were significantly decreased at 5 min of asphyxia in group HI-S and HI-M compared with group S and the baseline （P 〈0.05）.There were no Significant differences in MAP and arterial blood gas analysis at the each time point between group HI-S and HI-M （P 〉 0.05）. The density of viable neurons in putamen and candate nucleus was significantly lower, and NBS at 48-96 h after ROSC significantly higher in group HI-S and HI-M than＇in group S （ P 〈 0.05）. The density of viable neurons in putamen and caudate nucleus was Significantly higher and NBS at 72 and 96 h after ROSC significantly lower in group HI-M than in group HI-S （ P 〈 0.05）. Conclusion Midazolam used at the early stage of cardiopulmonary resuscitation can attenuate HI brain injury in neonatal piglets.