Department of Urology Surgery, Fourth Clinical Medical College, Guangzhou University of Chinese Medicine, Shenzhen, 518033, Guangdong, China.
Department of Anesthesiology, Fourth Clinical Medical College, Guangzhou University of Chinese Medicine, Shenzhen, 518033, Guangdong, China.
J Ethnopharmacol. 2020 Jan 10;246:112165. doi: 10.1016/j.jep.2019.112165. Epub 2019 Aug 21.
Blood-brain barrier (BBB) is a barrier which maintains the material exchange balance of brain microenvironment and could be destroyed by chronic stress (CS). Glucocorticoids (GCs) can mimic the chronic stress induced damage to BBB. GCs induced BBB trauma models in vitro and in vivo to explore the effects of the traditional medicine Xiao-Yao-San (XYS). In this research, we found CS could injure the BBB to change the biochemical index, which could be reversed by XYS in vitro. The abilities of cell proliferation, invasion, and the expression of tight junction related genes (Occludin, Claudin, JAM-1 and ZO-1) were suppressed by CS and the trauma could be reversed by XYS partly. It was showed that GRs interacted with Occludin directly and inhibited Occluding expression. In rats BBB trauma model, the GC content was deceased and BBB permeability was repaired by XYS. The expression of Occludin, Claudin, JAM-1 and ZO-1 were increased in the treatment of XYS. In our research, it shown that XYS affect the content of the GC and GR which interacted with Occludin directly for the first time. In addition, we also found that XYS could reduce BBB injury induced by CS via GR in BBB model in vitro. Therefore, it proves that XYS is a potential BBB repair medicine and may help to elucidate mechanism of brain pathology.
血脑屏障（BBB）是维持脑微环境物质交换平衡的屏障，可被慢性应激（CS）破坏。糖皮质激素（GCs）可模拟慢性应激对 BBB 的损伤。GCs 在体外和体内诱导 BBB 创伤模型，以探讨传统中药逍遥散（XYS）的作用。在这项研究中，我们发现 CS 可损伤 BBB 以改变生化指标，XYS 可在体外逆转这一损伤。CS 抑制细胞增殖、侵袭和紧密连接相关基因（Occludin、Claudin、JAM-1 和 ZO-1）的表达，XYS 可部分逆转这种损伤。研究表明，GR 与 Occludin 直接相互作用，抑制 Occluding 的表达。在大鼠 BBB 创伤模型中，XYS 降低 GC 含量并修复 BBB 通透性。XYS 治疗后 Occludin、Claudin、JAM-1 和 ZO-1 的表达增加。在我们的研究中，首次表明 XYS 影响与 Occludin 直接相互作用的 GC 和 GR 的含量。此外，我们还发现 XYS 可通过 GR 在体外 BBB 模型中减轻 CS 引起的 BBB 损伤。因此，这证明 XYS 是一种有潜力的 BBB 修复药物，可能有助于阐明脑病理学的机制。
