新生猪缺氧缺血性脑损伤时心肌线粒体的损伤

目的 了解缺氧缺血后新生猪心肌线粒体内钙离子浓度和呼吸链复合物N——细胞色素C氧化酶(CCO)活性的动态变化，探讨缺氧缺血性脑损伤(HIBD)发生时心肌细胞和胞内线粒体的损伤情况。方法 结扎新生猪左颈总动脉并缺氧2h，制成缺氧缺血性脑损伤模型，并设对照组。于恢复给氧后Oh、24h、48h、72h测定心肌线粒体内Ca^2 浓度和呼吸链复合物Ⅳ活性。结果 ①心肌线粒体Ca^2 含量升高，线粒体钙超载，复氧后48h和72h Ca^2 浓度逐步回降；②心肌线粒体呼吸链复合物IV活性下降，复氧后48h和72h；其活性回升，但72h仍未完全恢复正常；③线粒体Ca^2 浓度与呼吸链复合物Ⅳ活性呈直线负相关。结论 新生猪缺氧缺血性脑损伤发生时心肌细胞线粒体和呼吸链均受到损伤，随着复氧时间的延长损伤逐步恢复。缺氧缺血后心肌线粒体钙超载可能是线粒体呼吸链复合物Ⅳ活性下降的原因之一。

Injury of Myocardial Mitochondria in Neonatal Swines with Hypoxic-ischemic Brain Damage

OBJECTIVE: To clarify the effect of hypoxia and ischemia on the concentration of Ca2+ in myocardial mitochondria, and on the activity of respiratory chain complex IV--cytochrome oxidase (CCO) in neonatal swines, and to find out the change of myocardial mitochondria during hypoxic-ischemic brain damage (HIBD). METHODS: The study was performed on neonatal swines. For establishment of HIBD model, the left carotid was ligated and the swine was placed under hypoxia for two hours. Then the concentration of Ca2+ and the activity of respiratory chain complex IV in myocardial cell mitochondria were measured at 0 hour and 24, 48, 72 hours after reoxygenation. The measured values from these 0-, 24-, 48-, 72-hour-HIBD-groups (n = 10 per group) and from the normal control group (n = 10) were statistically analyzed by means of ANOVA, Newman-Keuls test and linear correlation. RESULTS: After the swines were placed under hypoxia-ischemia for two hours, 1. the concentration of Ca2+ in myocardial mitochondria increased, till 24 hours after re-oxygenation, and then it descended at 48 hours and 72 hours after reoxygenation; 2. the activity of myocardial mitochondrial respiratory chain complex IV descended, though activity recovery was seen at 48 and 72 hours, it did not come back to normal level at 72 hours after reoxygenation; 3. the concentration of Ca2+ in myocardial mitochondria was negatively correlated with the activity of respiratory chain complex IV. CONCLUSION: The results showed that in the neonatal swines with HIBD, the mitochondrial respiratory chain in myocardial cell was damaged by hypoxia-ischemia, yet it could be rehabilitated after reoxygenation. Calcium overload in myocardial mitochondria after hypoxia-ischemia might be one of the causes of the descending activity of respiratory chain complex IV.