朱国松 唐富东 王开伟

【摘要】目的 探讨线粒体动力相关蛋白1（Drp1）在大鼠术后认知功能障碍中的作用。方法 采用随机数表法将64只健康清洁级成年雄性SD大鼠分为生理盐水对照组（C组）、Drp1选择性抑制剂Mdivi-1腹腔注射组（M组）、手术组（O组）和Mdivi-1腹腔注射+手术组（MO组）。M组和MO组腹腔注射Mdivi-1（50 mg/kg）0.5 mL，C组和O组腹腔注射0.5 mL生理盐水。分别于术前、术后第1日和术后第3日进行水迷宫测试，观察大鼠的游泳距离和逃避潜伏期。术后24 h处死大鼠，取海马组织，检测其中三磷酸腺苷（ATP）含量，用透射电镜观察线粒体分裂情况，用蛋白免疫印迹法检查线粒体电子传递链复合物I和V的表达。结果 与C组比较，O组线粒体过度分裂，线粒体电子传递链复合物I和V水平下降，ATP含量减少，O组术后第1日和第3日逃避潜伏期及游泳距离延长（P均< 0.05）。与O组比较，MO组线粒体分裂减少，线粒体电子传递链复合物I和V水平升高，ATP含量增多;O组术后第1日和第3日逃避潜伏期及游泳距离缩短（P均< 0.05）。结论 线粒体Drp1介导的线粒体过度分裂参与了术后认知功能障碍的发生过程。

【關键词】线粒体;动力相关蛋白1;Mdivi-1;术后认知功能障碍

The role of mitochondrial dynamin-related protein 1 in postoperative  cognitive dysfunction in rat models Zhu Guosong， Tang Fudong， Wang Kaiwei. Department  of Anesthesiology and Perioperative Medicine， Henan Provincial Peoples Hospital，  Zhengzhou 450000， China

Corresponding author，Wang Kaiwei， E-mail： wangkw1975@163.com

【Abstract】Objective To investigate the role of mitochondrial dynamin-related protein 1 （Drp1） in postoperative cognitive dysfunction in rat models. Methods 64 healthy male Spragne-Dawley rats were randomly divided into the normal saline control group （group C）， Drp1 selective inhibitor Mdivi-1 intraperitoneal injection group （group M）， operation group （group O）， and Mdivi-1 intraperitoneal injection plus operation group （group MO） by using the random number table method. Mdivi-1 （50 mg/kg， 0.5 mL） was given via intraperitoneal injection in the M and MO groups. Normal saline（0.5 mL）was given in the C and O groups. Morris water maze test （MWN） was performed before operation， and 1 d and 3 d after operation. The escape latency and swimming distance were recorded. The animals were sacrificed at 24 h after operation. Hippocampal tissues were obtained for determination of ATP content. The mitochondrial division was observed by transmission electron microscopy. The expression levels of mitochondrial electron transport chain complex I and V were quantitatively measured by Western blot. Results Compared with the group C， mitochondrial division was significantly increased， and the expression levels of mitochondrial electron transport chain complex I and V were significantly down-regulated， the ATP content was significantly decreased， and the escape latency and swimming distance were significantly prolonged at postoperative 1 and 3 d in the group O （all P < 0.05）. Compared with the group O， mitochondrial division was significantly decreased， the expression levels of mitochondrial electron transport chain complex I and V were significantly up-regulated and the ATP content was significantly increased， the escape latency and swimming distance were significantly shortened at 1 and 3 d after operation in group MO （all P < 0.05）. Conclusion Excessive mitochondrial division mediated by Drp1 is involved in the pathogenesis of postoperative cognitive dysfunction.

【Key words】Mitochondrion; Dynamin-related protein 1; Mdivi-1;

Postoperative cognitive dysfunction

术后认知功能障碍（POCD）是一种术后比较常见的中枢神经系统并发症，在大、中型非心脏手术中，65岁以上患者的POCD发生率高达40%，在心脏手术中，该比例可高达60%，严重影响患者预后，因此探讨其发病机制意义重大[1-2]。研究表明能量代谢异常是引起认知功能障碍的关键因素之一，线粒体融合分裂失衡是线粒体功能损伤的标志性事件[3]。线粒体动力相关蛋白1（Drp1）是维持线粒体融合分裂平衡的重要因素。有学者发现，应用Drp1抑制剂抑制线粒体的过度分裂，维持线粒体的正常功能，能够治疗脑卒中、心肌梗死和神经退行性疾病。海马是与认知功能密切相关的脑区，海马组织中线粒体Drp1在POCD中的作用尚不明确。……