芬戈莫德给药可改善蛛网膜下腔出血小鼠的神经功能。
Fingolimod administration improves neurological functions of mice with subarachnoid hemorrhage.
机构信息
Department of Neurosurgery, Tianjin Medical University General Hospital, 154 Anshan Road, Tianjin, 300052, China; Tianjin Neurological Institute, Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education & Key Laboratory of Injuries, Variations and Regeneration of Nervous System, 154 Anshan Road, Tianjin, China.
Department of ICU, Tianjin Medical University General Hospital, 154 Anshan Road, Tianjin, 300052, China.
出版信息
Neurosci Lett. 2020 Sep 25;736:135250. doi: 10.1016/j.neulet.2020.135250. Epub 2020 Jul 13.
PURPOSE
To investigate the brain protective effects of fingolimod on inflammatory response of SAH mice.
METHODS
We utilized an endovascular mouse perforation model of SAH. Mice were divided into three groups: sham group, SAH group and SAH + Fingolimod group. Mice received either saline or fingolimod (1 mg/kg) intraperitoneally 2 h after sham surgery or SAH. The modified neurological severity score (mNSS) and Morris water maze were respectively used to evaluate the influence of nerve function. Evens blue (EB) extravasation was used to detect the permeability of blood-brain barrier, and water content in brain tissue was also detected. Flow cytometry, ELISA kits and western blotting were used to detect inflammatory factors in brain tissue.
RESULTS
The results showed that compared with SAH group, after treatment, the delay time of locating the hidden platform was shorter. The mNSS results showed that fingolimod improved the behavior of SAH mice. In addition, fingolimod could reduce the water content in brain. Flow cytometry results showed that after 3 d of treatment, fingolimod significantly increased Treg cells and down-regulated NK cells. Western blotting results showed fingolimod inhibited the expression of inflammatory cytokines in brain tissue. ELISA kit results showed that fingolimod could down-regulate IL-6 and TNF-α and up-regulate IL-10 and TGF-β1 in serum.
CONCLUSIONS
Fingolimod could regulate the inflammatory response to alleviate SAH-induced brain damage and promote neurological recovery, which provides a new therapeutic strategy for SAH treatment.
目的
研究芬戈莫德对蛛网膜下腔出血（SAH）小鼠炎症反应的脑保护作用。
方法
我们利用血管内小鼠 SAH 穿孔模型。将小鼠分为三组：假手术组、SAH 组和 SAH+芬戈莫德组。假手术后 2 h 内，各组小鼠分别接受生理盐水或芬戈莫德（1 mg/kg）腹腔内注射。改良神经功能严重程度评分（mNSS）和 Morris 水迷宫分别用于评估神经功能的影响。伊文思蓝（EB）外渗用于检测血脑屏障通透性，同时检测脑组织含水量。流式细胞术、ELISA 试剂盒和 Western blot 用于检测脑组织中的炎症因子。
结果
结果显示，与 SAH 组相比，治疗后，定位隐藏平台的延迟时间更短。mNSS 结果表明，芬戈莫德改善了 SAH 小鼠的行为。此外，芬戈莫德可降低脑组织含水量。流式细胞术结果显示，治疗 3 d 后，芬戈莫德显著增加 Treg 细胞，下调 NK 细胞。Western blot 结果表明，芬戈莫德抑制脑组织中炎症细胞因子的表达。ELISA 试剂盒结果表明，芬戈莫德可下调血清中 IL-6 和 TNF-α，上调 IL-10 和 TGF-β1。
结论
芬戈莫德可调节炎症反应，减轻 SAH 引起的脑损伤，促进神经功能恢复，为 SAH 治疗提供新的治疗策略。
Zotero 插件