State Key Laboratory of Natural Medicines, School of Basic Medical Sciences and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China.
State Key Laboratory of Natural Medicines, School of Basic Medical Sciences and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China.
Int Immunopharmacol. 2018 Apr;57:72-81. doi: 10.1016/j.intimp.2018.02.014. Epub 2018 Feb 22.
Cerebral ischemic and reperfusion injury often accompany with inflammation, and lead to severe neuronal damage, which further result in neurological disorders and memory disorders. In this study, we researched XQ-1H, a novel derivative of ginkgolide B, protecting against ischemic stroke in mice through regulation of microglia polarization. Middle cerebral artery occlusion (MCAO)/reperfusion in mice is applied to mimic ischemic stroke in vivo. Immediately after MCAO, mice are intragastric administrated with different dose (31 or 62 mg/kg) of XQ-1H for one or continuative three days. The in vivo experiments indicated that post-treatment with XQ-1H decreased cerebral infarction size, lessened brain edema, improved behavior and memory recover, inhibited pro-inflammatory and promoted anti-inflammatory cytokines expression and releasing in MCAO mice. Oxygen-glucose deprivation/reoxygenation (OGD/R) injury in BV-2 (microglia) cells is served in vitro. The in vitro findings revealed that incubation with XQ-1H protected against BV2 from OGD/R injury, regulated BV2 polarized from pro-inflammatory into anti-inflammatory phenotype, and promoted PPARγ mobilizing from nuclear to cytoplasm. In conclusion, the present study demonstrates that XQ-1H alleviated ischemic stroke by regulating balance of pro-/anti-inflammatory microglia polarization through PPARγ pathway both in vivo and in vitro, offering an alternative medication for stroke associated with inflammation.
脑缺血再灌注损伤常伴有炎症，并导致严重的神经元损伤，进而导致神经功能障碍和记忆障碍。在本研究中，我们研究了银杏内酯 B 的新型衍生物 XQ-1H，通过调节小胶质细胞极化来预防小鼠缺血性中风。应用大脑中动脉闭塞（MCAO）/再灌注在小鼠体内模拟缺血性中风。MCAO 后立即给予不同剂量（31 或 62mg/kg）的 XQ-1H 灌胃治疗 1 天或连续 3 天。体内实验表明，XQ-1H 治疗可减少脑梗死面积，减轻脑水肿，改善行为和记忆恢复，抑制促炎细胞因子表达和释放。在 BV-2（小胶质细胞）细胞中进行氧葡萄糖剥夺/再氧合（OGD/R）损伤。体外研究结果表明，XQ-1H 孵育可防止 BV2 发生 OGD/R 损伤，调节 BV2 从小胶质细胞的促炎表型向抗炎表型极化，并促进 PPARγ从核转移到细胞质。总之，本研究表明，XQ-1H 通过 PPARγ 通路调节促炎/抗炎小胶质细胞极化平衡，在体内和体外均减轻了缺血性中风，为与炎症相关的中风提供了一种替代药物。
