依达拉奉对毒死蜱所致大鼠脑损伤的保护作用及其机制*

doi:10.12047/j.cjap.6223.2022.024

摘要/Abstract

摘要： 目的: 探讨依达拉奉在毒死蜱诱导的神经元凋亡中的保护作用及其线粒体机制。方法: 在随机双盲的原则下,将大鼠分为对照组、毒死蜱组、依达拉奉组(n=6);以毒死蜱(18 mg/ 0.7 ml/ kg, sc.)造模,在注射毒死蜱1 h后用依达拉奉(10 mg/1.6 ml/kg, ip.)治疗。连续注射毒死蜱及依达拉奉28 d后,通过旷场和水迷宫试验测试大鼠学习记忆能力。在心脏灌流后取大鼠脑组织,通过HE染色检测大脑海马区的神经元损伤情况以及透射电子显微镜观察线粒体和细胞核损伤情况。测定Na⁺-K⁺-ATP酶、ATP含量判断线粒体损伤情况。用免疫组织化学和免疫印迹法测定线粒体分裂蛋白DRP1及DRP1的Ser 637位点磷酸化的表达。结果: 与对照组相比,毒死蜱组大鼠在旷场实验的3 min内的总运动距离和平均速度明显减小(P＜0.01),在水迷宫试验中的1 min内的逃避潜伏期明显延长、平台穿越次数明显减少(P＜0.01),脑组织的ATP酶活性明显降低(P＜0.01)且ATP含量下降(P＜ 0.05)、线粒体DRP1的Ser637位点磷酸化水平显著下降(P＜0.01);依达拉奉治疗后,大鼠在旷场试验中的运动总距离增大、平均速度增加(P＜0.05),在水迷宫试验中的潜伏期减短、穿越平台次数增加(P＜0.01),脑部病理切片显示神经细胞排列整齐、细胞核和线粒体损伤明显改善,脑组织的ATP酶活性升高(P＜0.01)、ATP水平上升(P＜ 0.05)、线粒体DRP1的Ser637位点磷酸化水平升高(P＜0.01)。结论: 依达拉奉通过促进DRP1的Ser637位点磷酸化的表达减轻毒死蜱所致大鼠脑损伤。

关键词: 毒死蜱, 依达拉奉, 动力相关蛋白1 (DRP1), 线粒体, 大鼠

Abstract: Objective: To investigate the protective effect of edaravone on chlorpyrifos-induced neuronal apoptosis and its mitochondrial mechanism. Methods: Under the principle of randomization and double-blindness, the rats were divided into control group, chlorpyrifos group, and edaravone group (n=6). The rats in edaravone group were treated with edaravone (10 mg/1.6 ml/kg, ip.) 1 h after chlorpyrifos injection. After continuous injection of chlorpyrifos and edaravone for 28 days, the learning and memory abilities of the rats were tested by open field and water maze tests. The rat brain tissue was collected after cardiac perfusion, and the neuronal damage in the hippocampus of the brain was detected by HE staining and the mitochondrial and nuclear damage were observed by transmission electron microscopy. The contents of Na⁺-K⁺-ATPase and ATP were measured to evaluate mitochondrial damage. The expression of mitochondrial fission protein DRP1 and phosphorylation at Ser 637 of DRP1 were determined by immunohistochemistry and immunoblotting. Results: Compared with the control group, the total movement distance and average speed of the rats in the chlorpyrifos group were decreased significantly within 3 minutes of the open field test (P＜0.01), and the escape latency within 1 minute of the water maze test was prolonged significantly. The number of platform crossings was reduced significantly (P＜0.01), the activity of ATPase in brain tissue was decreased significantly (P＜0.01) , the content of ATP and the phosphorylation level of Ser637 of mitochondrial DRP1 were decreased significantly (P＜0.05, P＜0.01). After edaravone treatment, the total movement distance and average speed of rats in the open field test were increased (P＜0.05), the latency in the water maze test was decreased, and the number of crossing platforms was increased (P＜0.01), brain pathological sections showed that nerve cells were arranged neatly, nucleus and mitochondrial damage was significantly improved, the activity of ATPase in brain tissue was increased (P＜0.01), the levels of ATP and mitochondrial DRP1 Ser637 phosphorylation increased (P＜0.05, P＜0.01).Conclusion: Edaravone alleviates chlorpyrifos-induced brain injury in rats by promoting the phosphorylation of DRP1 at Ser637.

Key words: chlorpyrifos, edaravone, dynamin-related protein 1(DRP1), mitochondrial, rat

中图分类号:

林佩瑶, 宋英, 秦东旭, 卢栋泽, 范徐丽. 依达拉奉对毒死蜱所致大鼠脑损伤的保护作用及其机制^*[J]. 中国应用生理学杂志, 2022, 38(2): 163-168.

LIN Pei-yao, SONG Ying, QIN Dong-xu, LU Dong-ze, FAN Xyu-li. Protective effect of edaravone on chlorpyrifos-induced brain injury in rats and its mechanism[J]. CJAP, 2022, 38(2): 163-168.

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依达拉奉对毒死蜱所致大鼠脑损伤的保护作用及其机制^*

Protective effect of edaravone on chlorpyrifos-induced brain injury in rats and its mechanism

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