Lin Pei-Yao, Song Ying, Qin Dong-Xu, Lu Dong-Ze, Fan Xyu-Li
Department of Pharmacology, Zhejiang University of Technology, Hangzhou 310014, China.
Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2022 Mar;38(2):163-168. doi: 10.12047/j.cjap.6223.2022.024.
To investigate the protective effect of edaravone on chlorpyrifos-induced neuronal apoptosis and its mitochondrial mechanism. Under the principle of randomization and double-blindness, the rats were divided into control group, chlorpyrifos group, and edaravone group (=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. 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 (＜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 (＜0.01), the activity of ATPase in brain tissue was decreased significantly (＜0.01) , the content of ATP and the phosphorylation level of Ser637 of mitochondrial DRP1 were decreased significantly (＜0.05, ＜0.01). After edaravone treatment, the total movement distance and average speed of rats in the open field test were increased (＜0.05), the latency in the water maze test was decreased, and the number of crossing platforms was increased (＜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 (＜0.01), the levels of ATP and mitochondrial DRP1 Ser637 phosphorylation increased (＜0.05, ＜0.01). Edaravone alleviates chlorpyrifos-induced brain injury in rats by promoting the phosphorylation of DRP1 at Ser637.
探讨依达拉奉对毒死蜱诱导的神经元凋亡的保护作用及其线粒体机制。按照随机双盲原则，将大鼠分为对照组、毒死蜱组和依达拉奉组（每组(n = 6)）。依达拉奉组大鼠在注射毒死蜱(1)小时后腹腔注射依达拉奉（(10 mg/1.6 ml/kg)）。连续注射毒死蜱和依达拉奉(28)天后，通过旷场试验和水迷宫试验检测大鼠的学习和记忆能力。心脏灌注后采集大鼠脑组织，通过苏木精-伊红（HE）染色检测脑内海马区的神经元损伤情况，并用透射电子显微镜观察线粒体和细胞核损伤情况。检测钠钾-ATP酶和ATP含量以评估线粒体损伤。通过免疫组织化学和免疫印迹法检测线粒体分裂蛋白动力相关蛋白(1)（DRP1）的表达及其丝氨酸(637)位点的磷酸化水平。与对照组相比，毒死蜱组大鼠在旷场试验(3)分钟内的总运动距离和平均速度显著降低（(P＜0.01)），水迷宫试验(1)分钟内的逃避潜伏期显著延长，穿越平台次数显著减少（(P＜0.01)），脑组织中ATP酶活性显著降低（(P＜0.01)），ATP含量以及线粒体DRP1丝氨酸(637)位点的磷酸化水平显著降低（(P＜0.05)，(P＜0.01)）。依达拉奉治疗后，大鼠在旷场试验中的总运动距离和平均速度增加（(P＜0.05)），水迷宫试验中的潜伏期缩短，穿越平台次数增加（(P＜0.01)），脑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，脑组织中ATP酶活性增加（(P＜0.01)），ATP水平以及线粒体DRP1丝氨酸(637)位点的磷酸化水平升高（(P＜0.05)，(P＜0.01)）。依达拉奉通过促进DRP1丝氨酸(637)位点的磷酸化减轻毒死蜱诱导的大鼠脑损伤。
