Shen Jian, Huang Kaiyuan, Zhu Yu, Xu Kangli, Zhan Renya, Pan Jianwei
Departments of Neurosurgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
Evid Based Complement Alternat Med. 2020 Jul 31;2020:5264205. doi: 10.1155/2020/5264205. eCollection 2020.
Buyang Huanwu decoction (BYHWD), an important traditional Chinese medicine (TCM), has been used clinically for centuries for the treatment of various diseases. The study aims to explore the BYHWD effects on angiogenesis and neuroprotection after cerebral ischemia/reperfusion (CI/R) injury in rats and to explore the underlying angiogenic roles and mechanisms of BYHWD in hydrogen peroxide (HO) induced oxidative stress in human umbilical vein endothelial cells (HUVECs) model.
The effects of BYHWD on neurological function were screened by measuring neurological deficits, spatial memory function, and angiogenesis (by microvascular density (MVD) and cerebral blood flow (CBF)) after CI/R injury in middle cerebral artery occlusion (MCAO) in vivo in rats. In vitro, we examined the angiogenic roles and mechanisms of action of BYHWD in an HO-induced oxidative stress HUVECs model by measuring cell viability, apoptosis, vascular tube formation, intracellular ROS generation, NADPH oxidase (Nox) activity, and Nox4 protein expression.
BYHWD significantly improved neurological function, including neurological deficits and spatial learning and memory, and significantly increased MVD and CBF in the ischemic penumbra after CI/R injury in rats. BYHWD significantly increased cell viability, inhibited apoptosis, induced vascular tube formation, decreased intracellular ROS generation, and reduced Nox activity and Nox4 protein expression in HO-treated HUVECs in a dose-dependent manner.
Our study demonstrates that BYHWD promotes neurological function recovery and increases angiogenesis. BYHWD exerts angiogenic effects against cerebral ischemic injury through the downregulation of Nox4, which results in the reduction of ROS generation.
补阳还五汤（BYHWD）是一种重要的传统中药，已在临床上应用数百年，用于治疗各种疾病。本研究旨在探讨补阳还五汤对大鼠脑缺血/再灌注（CI/R）损伤后血管生成和神经保护的作用，并探讨补阳还五汤在过氧化氢（HO）诱导的人脐静脉内皮细胞（HUVECs）氧化应激模型中的潜在血管生成作用及机制。
通过测量大鼠大脑中动脉闭塞（MCAO）模型CI/R损伤后的神经功能缺损、空间记忆功能和血管生成（通过微血管密度（MVD）和脑血流量（CBF）），筛选补阳还五汤对神经功能的影响。在体外，我们通过测量细胞活力、凋亡、血管管形成、细胞内活性氧生成、NADPH氧化酶（Nox）活性和Nox4蛋白表达，研究补阳还五汤在HO诱导的氧化应激HUVECs模型中的血管生成作用及作用机制。
补阳还五汤显著改善神经功能，包括神经功能缺损以及空间学习和记忆能力，并显著增加大鼠CI/R损伤后缺血半暗带的MVD和CBF。补阳还五汤显著增加HO处理的HUVECs的细胞活力，抑制凋亡，诱导血管管形成，降低细胞内活性氧生成，并以剂量依赖性方式降低Nox活性和Nox4蛋白表达。
我们的研究表明，补阳还五汤促进神经功能恢复并增加血管生成。补阳还五汤通过下调Nox4发挥抗脑缺血损伤的血管生成作用，从而减少活性氧的生成。
