长期补充低剂量褪黑素对大鼠心跳骤停后线粒体功能的保护作用

Protective Effect of Long-Term Low-Dose Melatonin Supplementation on Mitochondrial Function after Cardiac Arrest in Rats

摘要: 目的：通过长期服用保健药物来预防心跳骤停诱发的死亡是错综复杂且较少探索的复苏策略。褪黑激素是一种改善睡眠的保健品，有研究报道其在冬眠动物的唤醒期不断升高，在血液回流后可以提高存活率，并减少再灌注损伤。本研究旨在探索每日预防性补充保健药物褪黑激素对减少心跳骤停危害的影响。方法：研究对象为SD雄性大鼠，240~340克。共分为3组：对照组(Sham组)；心跳骤停组(CA组)；和药物预处理组(Mel组)。Mel组，大鼠每天接受腹腔注射10 mg/kg的褪黑素，持续14天。8分钟窒息诱导心跳骤停后进行手动心肺复苏。复苏后24小时进行神经学评分，取海马组织观测线粒体的完整性、动力学改变和功能损伤。结果：Mel组的存活率高于CA组(38.89% vs. 31.81%, P = 0.641)。ΔΨm在CA组、Mel组低于Sham组(P < 0.05)。ROS、线粒体肿胀和线粒体呼吸速率在CA组低于Sham组(P < 0.05)。ΔΨm、线粒体肿胀、线粒体呼吸速率在Mel组高于CA组(P > 0.05)。ROS在Mel组低于CA组(P = 0.535)。结论：心跳骤停复苏后加重了线粒体损伤。长期补充低剂量褪黑素改善了大鼠心跳骤停后线粒体功能。

Abstract: Objective: Prophylactic pharmacotherapy for health care in reducing death after cardiac arrest (CA) is an elusive and less explored strategy. Melatonin, a natural health product contributing to sleep, was elevated upon arousal from torpor in hibernating mammals, which increased survival after blood return and reduced reperfusion injury. In this study, we sought to find the effects of long-term daily prophylactic supplement with melatonin as a health care medicine on the victim of CA. Meth-ods: SD rats, 240~340 g, were used in this study. Sham, CA, and melatonin + CA (Mel) groups were included. The rats in the Mel group received daily IP injection of melatonin 10 mg/kg for 14 days. CA was induced by 8 mins asphyxia and followed by manual CPR. The endpoint was 24 h after re-suscitation. Neurological outcome was assessed. Hippocampal mitochondrial function was observed. Results: Survival in the Mel group was higher than in the CA group (38.89% vs. 31.81%, P = 0.641). ΔΨm was lower in the CA group and Mel group than in the Sham group (P < 0.05). ΔΨm, mitochon-drial swelling and mitochondria respiratory rate were higher in the Mel group than in the CA group (P > 0.05). ROS production was lower in the Mel group (P = 0.535). Conclusions: CA induced mito-chondrial injury. Long-term daily prophylactic supplement with low dosage of melatonin improved neuronal mitochondrial function after CA.