Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, Dali University, Dali, China.
Department of Neurosurgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xia Men, China.
Neuropeptides. 2024 Oct;107:102462. doi: 10.1016/j.npep.2024.102462. Epub 2024 Aug 13.
In this study, we explored the neuroprotective effect of melittin (MEL) after brain ischemia using a rat model.
The rats underwent middle cerebral artery occlusion (MCAO) for 60 min and were randomly divided into the control group, saline group, and MEL group. Rats in each group were injected intraperitoneally with MEL one day before MCAO until sacrificed. Morris water maze and rotation test were used to assess locomotor function and cognitive ability. The 9.4 Tesla MRI was used to scan and assess the infarct volume of the rat brains. Immunohistochemistry was used to detect the sites of action of MEL on microglia. Western blot and ELISA were used to measure the effect of MEL on the production of pro-inflammatory cytokines. The effect of MEL on neuronal cell apoptosis was observed by flow cytometry.
Compared with the saline group, MEL treatment significantly increased the density of neurons in the cerebral cortical and reduced the cerebral infarct size after MCAO (33.9 ± 8.8% vs. 15.8 ± 3.9%, P < 0.05). Meanwhile, the time for MEL-treated rats to complete the water maze task on the 11th day after MCAO was significantly shorter than that of rats in the saline group (P < 0.05). MEL treatment also prolonged the rotarod retention time on day 14 after MCAO. Immunohistochemistry analysis showed that MEL inhibited the activation of microglia and suppressed the expression of TNF-α, IL-6, and IL-1β in the brain after ischemia. MEL treatment resulted in a significant decrease in TLR4, MyD88, and NF-κB p65 levels in extracts from the ischemic cerebral cortex. Finally, MEL reduced neuronal apoptosis induced by ischemic stroke (P < 0.05).
MEL treatment promotes neurological function recovery after cerebral ischemia in rats. These effects are potentially mediated through anti-inflammatory and anti-apoptotic mechanisms.
本研究旨在通过大鼠模型探讨蜂毒素（MEL）在脑缺血后的神经保护作用。
大鼠进行大脑中动脉阻塞（MCAO） 60 分钟，随机分为对照组、盐水组和 MEL 组。每组大鼠在 MCAO 前一天腹腔注射 MEL，直至处死。Morris 水迷宫和旋转试验用于评估运动功能和认知能力。9.4T MRI 用于扫描和评估大鼠脑梗死体积。免疫组织化学用于检测 MEL 在小胶质细胞上的作用部位。Western blot 和 ELISA 用于测量 MEL 对促炎细胞因子产生的影响。流式细胞术观察 MEL 对神经元细胞凋亡的影响。
与盐水组相比，MEL 治疗显著增加了大脑皮质神经元的密度，并减少了 MCAO 后的脑梗死面积（33.9±8.8%比 15.8±3.9%，P<0.05）。同时，MEL 治疗组大鼠在 MCAO 后第 11 天完成水迷宫任务的时间明显短于盐水组（P<0.05）。MEL 治疗还延长了 MCAO 后第 14 天的旋转棒保留时间。免疫组织化学分析显示，MEL 抑制了缺血后小胶质细胞的激活，并抑制了大脑中 TNF-α、IL-6 和 IL-1β 的表达。MEL 治疗导致缺血性大脑皮质提取物中 TLR4、MyD88 和 NF-κB p65 水平显著降低。最后，MEL 减少了缺血性中风诱导的神经元凋亡（P<0.05）。
MEL 治疗促进了大鼠脑缺血后神经功能的恢复。这些作用可能是通过抗炎和抗凋亡机制介导的。
