Department of Encephalopathy, Hubei Provincial Traditional Chinese Medicine Hospital, Wuhan, People's Republic of China.
Department of Encephalopathy, Hubei Institute of Traditional Chinese Medicine, Wuhan, People's Republic of China.
Hum Cell. 2019 Jan;32(1):22-30. doi: 10.1007/s13577-018-0220-3. Epub 2018 Nov 1.
Cerebrovascular smooth muscle cells (SMCs) hyperplasia is an important contributor to cerebrovascular remodeling during hypertension. The aim of present study was to investigate the effects of Icariin on cerebrovascular SMCs proliferation and remodeling and the underlying mechanisms. The results revealed that Icariin administration attenuated the enhanced basilar artery constriction in angiotensin II (AngII)-induced hypertension rat model, as well as the inhibition of basilar artery diameter reduction in response to AngII and phenylephrine. In addition, histological analyses showed that Icariin also significantly ameliorated basilar artery remodeling in AngII hypertensive rats. In human brain vascular SMCs (HBVSMCs), AngII-induced cell proliferation, migration and invasion were markedly inhibited by Icariin treatment. Moreover, Icariin treatment largely limited AngII-induced the increase of reactive oxygen species (ROS) production in HBVSMCs, which was closely associated with cell proliferation. Analysis of the mechanisms showed that Icariin decreased ROS production via inhibiting NADPH oxidase activity but not mitochondria-derived ROS production. Further, Icariin promoted Nox2 degradation and consequently reduced its protein expression. In conclusion, these findings demonstrate that Icariin attenuates cerebrovascular SMCs hyperplasia and subsequent remodeling through inhibiting Nox2-containing NADPH oxidase activation, suggesting Icariin may be a potential therapeutic agent to prevent the onset and progression of stroke.
脑血管平滑肌细胞（SMC）增生是高血压期间脑血管重塑的重要因素。本研究旨在探讨淫羊藿苷对脑血管 SMC 增殖和重塑的影响及其潜在机制。结果表明，淫羊藿苷可减轻血管紧张素 II（AngII）诱导的高血压大鼠模型基底动脉收缩增强，以及对 AngII 和苯肾上腺素反应的基底动脉直径减小的抑制作用。此外，组织学分析表明，淫羊藿苷还可显著改善 AngII 高血压大鼠的基底动脉重塑。在人脑血管平滑肌细胞（HBVSMC）中，淫羊藿苷处理可明显抑制 AngII 诱导的细胞增殖、迁移和侵袭。此外，淫羊藿苷处理可显著限制 AngII 诱导的 HBVSMC 中活性氧（ROS）产生的增加，这与细胞增殖密切相关。机制分析表明，淫羊藿苷通过抑制 NADPH 氧化酶活性而不是线粒体来源的 ROS 产生来减少 ROS 产生。此外，淫羊藿苷促进 Nox2 降解，从而降低其蛋白表达。总之，这些发现表明，淫羊藿苷通过抑制含 Nox2 的 NADPH 氧化酶的激活来减轻脑血管 SMC 的增生和随后的重塑，提示淫羊藿苷可能是预防中风发生和进展的潜在治疗剂。
