Translational Medicine Center of Pain, Emotion and Cognition, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo 315211, China.
School of Materials Science and Chemical Engineering, Ningbo University, Ningbo 315211, China.
Int Immunopharmacol. 2021 Aug;97:107656. doi: 10.1016/j.intimp.2021.107656. Epub 2021 Apr 23.
This study was aimed to investigate the neuroprotective effects of 9-methylfascaplysin, a novel marine derivative derived from sponge, against middle cerebral artery occlusion/reperfusion (MCAO)-induced motor impairments, neuroinflammation and oxidative stress in rats.
Neurological and behavioral tests were used to evaluate behavioral changes. The 2, 3, 5-triphenyltetrazolium chloride staining was used to determine infarct size and edema extent. Activated microglia/macrophage was analyzed by immunohistochemical staining of Iba-1. RT-PCR and ELISA were used to measure the expression of inducible nitric oxide synthase, tumor necrosis factor-α, interleukin-1β, CD16 and CD206. Western blotting analysis was performed to explore the activation of nuclear factor-κB (NF-κB) and NLRP3. The levels of oxidative stress were studied by evaluating the activities of superoxide dismutase, catalase and glutathione peroxidase.
Post-occlusion intracerebroventricular injection of 9-methylfascaplysin significantly attenuated motor impairments and infarct size in MCAO rats. Moreover, 9-methylfascaplysin reduced the activation of microglia/macrophage in ischemic penumbra as evidenced by the decreased Iba-1-positive area and the reduced expression of pro-inflammatory factors. Furthermore, 9-methylfascaplysin inhibited MCAO-induced oxidative stress and activation of NF-κB and NLRP3 inflammasome.
All the results suggested that 9-methylfascaplysin might produce neuroprotective effects against MCAO via the reduction of oxidative stress and neuroinflammation, simultaneously, possibly via the inhibition of NF-κB and NLRP3 inflammasome.
本研究旨在探讨海绵来源的新型海洋衍生物 9-甲基海鞘素对大鼠大脑中动脉闭塞/再灌注（MCAO）引起的运动障碍、神经炎症和氧化应激的神经保护作用。
采用神经学和行为学测试评估行为变化。2,3,5-三苯基氯化四氮唑染色法测定梗死面积和水肿程度。通过 Iba-1 免疫组织化学染色分析活化的小胶质细胞/巨噬细胞。逆转录聚合酶链反应和酶联免疫吸附试验用于测量诱导型一氧化氮合酶、肿瘤坏死因子-α、白细胞介素-1β、CD16 和 CD206 的表达。Western blot 分析用于研究核因子-κB（NF-κB）和 NLRP3 的激活。通过评估超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶的活性来研究氧化应激水平。
MCAO 大鼠脑室内注射 9-甲基海鞘素后，运动障碍和梗死面积明显减轻。此外，9-甲基海鞘素减少了缺血半影区小胶质细胞/巨噬细胞的活化，表现为 Iba-1 阳性面积减少和促炎因子表达降低。此外，9-甲基海鞘素抑制了 MCAO 诱导的氧化应激和 NF-κB 和 NLRP3 炎性小体的激活。
所有结果表明，9-甲基海鞘素可能通过减轻氧化应激和神经炎症产生对 MCAO 的神经保护作用，同时可能通过抑制 NF-κB 和 NLRP3 炎性小体来实现。
