Department of Physiology, School of Basic Medical Science, Guangzhou University of Chinese Medicine, Guangzhou, China.
Medical School, South China University of Technology, Guangzhou, China.
Chin J Physiol. 2022 Mar-Apr;65(2):72-79. doi: 10.4103/cjp.cjp_94_21.
Buyang Huanwu decoction (BYHWD), a classical prescription for ischemic stroke, has been reported to promote angiogenesis after focal ischemia. However, the mechanisms of the contribution of BYHWD on angiogenesis are still unclear. Connexin 43 (Cx43) played important roles in the functions of neurogliovascular unit. Therefore, the aim of this study was to explore the potential role of Cx43 in angiogenesis of the ischemic brain after BYHWD treatment. Middle cerebral artery occlusion (MCAO) was used to establish the model of focal ischemia. BYHWD was administrated intragastrically twice a day after MCAO with or without Gap26 (a specific Cx43 inhibitor). Western blot, neurological deficits, immunofluorescent staining, and Evans blue dye were used to confirm the role of Cx43 in angiogenesis after BYHWD treatment. The expression levels of total Cx43 and phosphorylated Cx43 were upregulated by BYHWD and peaked at 7 days post MCAO. Inhibition of Cx43 with Gap26 significantly attenuated the protective role of BYHWD in neurological behavior. BYHWD treatment promoted angiogenesis demonstrated by increased microvascular density, upregulated vascular endothelial growth factor (VEGF), and angiopoietin-1 (Ang-1), while inhibition of Cx43 with Gap26 attenuated these effects of BYHWD. In addition, Gap26 inhibited the beneficial effect of BYHWD on blood-brain barrier (BBB) integrity. These results suggested that Cx43 mediated the angiogenesis of BYHWD via VEGF and Ang-1 after focal ischemic stroke.
补阳还五汤（BYHWD）是一种治疗缺血性中风的经典方剂，据报道它能促进局灶性缺血后的血管生成。然而，BYHWD 促进血管生成的机制仍不清楚。连接蛋白 43（Cx43）在神经胶质血管单元的功能中起着重要作用。因此，本研究旨在探讨 Cx43 在 BYHWD 治疗缺血性脑后血管生成中的潜在作用。大脑中动脉闭塞（MCAO）用于建立局灶性缺血模型。MCAO 后，BYHWD 每天两次灌胃，同时或不使用 Gap26（一种特定的 Cx43 抑制剂）。Western blot、神经功能缺损、免疫荧光染色和 Evans 蓝染料用于证实 Cx43 在 BYHWD 治疗后血管生成中的作用。总 Cx43 和磷酸化 Cx43 的表达水平被 BYHWD 上调，并在 MCAO 后 7 天达到峰值。用 Gap26 抑制 Cx43 显著减弱了 BYHWD 在神经行为中的保护作用。BYHWD 治疗促进血管生成，表现为微血管密度增加、血管内皮生长因子（VEGF）和血管生成素-1（Ang-1）上调，而用 Gap26 抑制 Cx43 则减弱了 BYHWD 的这些作用。此外，Gap26 抑制了 BYHWD 对血脑屏障（BBB）完整性的有益作用。这些结果表明，Cx43 通过 VEGF 和 Ang-1 介导了局灶性缺血后 BYHWD 的血管生成。
