评价不同剂量的HOE-642对大鼠心脏骤停后神经线粒体功能的保护作用

The Effects of Different Doses of HOE-642 for the Protection of Neuronal Mitochondrial Function after Cardiac Arrest in Rats

摘要: 目的：评价不同剂量的HOE-642对大鼠心脏骤停后神经线粒体功能的保护作用。方法：大鼠采用窒息性心脏骤停，8 min后进行心肺复苏。共分为6组：常温组(N组)；HOE-642用药组(HOE组)，在开始复苏前分别静脉注射HOE-642 1 mg/kg或5 mg/kg；低温组(Hypo组)，在恢复血流后采用中度低温(33℃ ± 0.5℃)治疗；低温复合HOE-642用药组(Hypo + HOE组)，在开始进行复苏前分别静脉注射HOE-642 1 mg/kg或5 mg/kg，并在循环恢复后采用中度低温治疗。成功复苏后24 h，计算大鼠的存活率，并进行神经功能损伤的评估(NDS)。其后提取大鼠的海马组织并分离线粒体以测量线粒功能。结果：在复苏24 h后，大鼠的存活率在Hypo + HOE 1 mg组明显比N组和HOE 1 mg组高(P < 0.05)；NDS在Hypo + HOE 1 mg组明显比N组低(P < 0.05)；线粒体的功能在Hypo + HOE 1 mg组明显优于Hypo + HOE 5 mg组。结论：相比于HOE-642，5 mg/kg的剂量，在开始复苏时静注HOE-642，1 mg/kg的剂量对神经线粒体的功能更有益。

Abstract: Objective: This study was to explore the effects of different doses of HOE-642 for the protection of neuronal mitochondrial function after cardiac arrest in rats. Methods: Cardiac arrest was induced by 8 min of asphyxia in rats. Six groups were included: N group, normothermia; HOE groups, HOE-642 1 or 5 mg/kg, iv, when initiating CPR; Hypo group, mild hypothermia (33˚C ± 0.5˚C) in-duced following the return of spontaneous circulation; Hypo + HOE groups, HOE-642, 1 or 5 mg/kg, plus mild hypothermia. Survival and NDS were evaluated after 24 h of resuscitation. Mitochondrial function of the hippocampus was detected. Results: Survival in the Hypo + HOE 1 mg group was the best and significantly higher than in the N and HOE 1 mg groups (P < 0.05). NDS in the Hypo + HOE 1 mg group was significantly lower than in the N group (P < 0.05). The mitochondrial function in the Hypo + HOE 1 mg group was better than in the Hypo + HOE 5 mg group. Conclusions: HOE-642 1 mg/kg was beneficial compared to HOE-642 5 mg/kg used when initiating resuscitation for the protection of neuronal mitochondrial function after cardiac arrest.