Zhuang Jianfeng, Peng Yucong, Gu Chi, Chen Huihui, Lin Zheng, Zhou Hang, Wu Xiao, Li Jianru, Yu Xiaobo, Cao Yang, Zeng Hanhai, Fu Xiongjie, Xu Chaoran, Huang Peiyu, Cao Shenglong, Wang Chun, Yan Feng, Chen Gao
Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Jiefang Road 88th, Hangzhou, China.
Department of Radiology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
Transl Stroke Res. 2021 Aug;12(4):660-675. doi: 10.1007/s12975-020-00842-9. Epub 2020 Sep 12.
Intracerebral hemorrhage (ICH) is a cerebrovascular disease with high mortality and morbidity for which effective treatments are currently lacking. Wogonin is a major flavonoid compound isolated from Scutellaria radix. Accumulating evidence suggests that wogonin plays a crucial role in anti-inflammatory and anti-oxidative stress. Treatment of microglia with nuclear receptor agonists augments the expression of phagocytosis-related genes. However, the neuroprotective effects of wogonin in ICH remain obscure. In this study, we elucidated an innovative mechanism by which wogonin acts to enhance phagocytosis in a murine model of ICH. Wogonin promoted hematoma clearance and improved neurological recovery after ICH by upregulating the expression of Axl, MerTK, CD36, and LAMP2 in perihematomal microglia and BV2 cells. Treatment of a murine model of ICH with wogonin stimulated microglial phagocytosis in vitro. Further, we demonstrated that wogonin dramatically attenuated inflammatory and oxidative stress responses in a murine model of ICH by reducing the expression of pro-inflammatory cytokines and pro-oxidant enzymes such as TNF-α, IL-1β, and inducible nitric oxide synthase (iNOS) after ICH. The effects of wogonin were abolished by administration of the PPAR-γ inhibitor GW9662. In conclusion, our data suggest that wogonin facilitates hematoma clearance and neurobehavioral recovery by targeting PPAR-γ.
脑出血（ICH）是一种死亡率和发病率都很高的脑血管疾病，目前缺乏有效的治疗方法。汉黄芩素是从黄芩中分离出的一种主要黄酮类化合物。越来越多的证据表明，汉黄芩素在抗炎和抗氧化应激中起关键作用。用核受体激动剂处理小胶质细胞可增强吞噬相关基因的表达。然而，汉黄芩素在脑出血中的神经保护作用仍不清楚。在本研究中，我们阐明了一种创新机制，即汉黄芩素在脑出血小鼠模型中通过该机制增强吞噬作用。汉黄芩素通过上调血肿周围小胶质细胞和BV2细胞中Axl、MerTK、CD36和LAMP2的表达，促进脑出血后的血肿清除并改善神经功能恢复。用汉黄芩素处理脑出血小鼠模型可在体外刺激小胶质细胞吞噬作用。此外，我们证明，汉黄芩素通过降低脑出血后促炎细胞因子和促氧化酶如TNF-α、IL-1β和诱导型一氧化氮合酶（iNOS）的表达，显著减轻脑出血小鼠模型中的炎症和氧化应激反应。给予PPAR-γ抑制剂GW9662可消除汉黄芩素的作用。总之，我们的数据表明，汉黄芩素通过靶向PPAR-γ促进血肿清除和神经行为恢复。
