Goreisan inhibits vascular endothelial cell migration and angiogenesis
Goreisan inhibits vascular endothelial cell migration and angiogenesis
复制标题
DOI：
10.1002/tkm2.1275
复制
发表时间：
2021-04-01
期刊：
影响因子：
--
通讯作者：
Isohama, Yoichiro
中科院分区：
文献类型：
--
作者：
Murakami, Kazuhito;Horie, Ichiro;Isohama, Yoichiro
目的：Goreisan（GRS）是一种日本汉方药，临床上用于治疗水肿和头痛。最近，一项临床研究表明GRS可显着抑制慢性硬膜下血肿（CSDH）的复发。在CSDH中，新膜上未成熟血管的渗漏与复发或恶化有关。尽管一些临床报告显示了 GRS 的有效性，但 GRS 的药理学特性和潜在机制尚不清楚。本研究通过体外和体内实验探讨GRS对血管内皮细胞迁移和增殖的影响。方法：用血管内皮生长因子（VEGF）处理人脐血管内皮细胞（HUVEC）24 h，测定迁移能力、细胞外信号调节激酶（ERK）磷酸化水平和水通道蛋白-1（AQP1）表达水平。将含有 VEGF 的基质胶皮下注射到 C57BL 小鼠的腹部（基质胶塞测定）。口服GRS 7天后，通过免疫染色检测对血管生成的影响。结果：GRS以剂量依赖性方式抑制VEGF诱导的迁移。 GRS 还抑制 VEGF 诱导的 ERK 磷酸化，ERK 是迁移的主要信号分子。此外，GRS 显着降低 AQP1 的蛋白和 mRNA 表达，AQP1 是内皮细胞迁移的另一个重要调节因子。最后，体内Matrigel栓塞实验显示，GRS抑制血管生成。结论：研究结果表明，GRS可以通过下调ERK活化和aquaporin-1表达来抑制内皮细胞迁移，从而抑制血管生成，从而对CSDH复发具有预防作用。
Aim: Goreisan (GRS) is a Japanese Kampo medicine, which has been clinically used to treat edema and headache. Recently, a clinical study indicated that GRS significantly suppresses the recurrence of chronic subdural hematoma (CSDH). In CSDH, leakage from immature blood vessels on the neomembrane is involved in the recurrence or exacerbation. Although several clinical reports have shown the effectiveness of GRS, the pharmacological properties and underlining mechanism of GRS are not clear. In this study, we examined the effect of GRS on the migration and proliferation of vascular endothelial cells via in vitro and in vivo experiments.Method: Human umbilical vascular endothelial cells (HUVECs) were treated with vascular endothelial growth factor (VEGF) for 24 h, and migration ability, extracellular signal-regulated kinase (ERK) phosphorylation level, and aquaporin-1 (AQP1) expression level were measured. Matrigel containing VEGF was injected subcutaneously into the abdomen of C57BL mice (Matrigel plug assay). After oral administration of GRS for seven days, the effect on angiogenesis was examined by immunostaining.Results: GRS inhibited VEGF-induced migration in a dose-dependent manner. GRS also inhibited VEGF-induced phosphorylation of ERK, which is a major signaling molecule for the migration. In addition, GRS markedly decreased protein and mRNA expression of AQP1, which is another important regulator of endothelial cell migration. Finally, GRS inhibited angiogenesis, as revealed by in vivo Matrigel plug assay.Conclusion: The findings indicated that GRS can suppress angiogenesis through inhibiting the migration of endothelial cells by downregulating ERK activation and aquaporin-1 expression, leading to the preventive effect of GRS against CSDH recurrence.