Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, People's Republic of China.
Drug Des Devel Ther. 2020 Feb 28;14:933-947. doi: 10.2147/DDDT.S229302. eCollection 2020.
Traditional Chinese medicine (TCM) provides unique advantages for treatment of ischemic stroke, an aging-related vascular disease. Shengmai powder (GRS) is composed of three active components, specifically, ginsenoside Rb1, ruscogenin and schisandrin A, at a ratio of 6:0.75:6. The main objective of this study was to evaluate the effects of GRS on blood-brain barrier (BBB) dysfunction under conditions of middle cerebral artery occlusion/reperfusion (MCAO/R).
C57BL/6J mice subjected to MCAO/R were used as a model to assess the protective effects of varying doses of GRS (6.4, 12.8, and 19.2 mg/kg) on BBB dysfunction.
GRS reduced cerebral infarct volume and degree of brain tissue damage, improved behavioral scores, decreased water content and BBB permeability, and restored cerebral blood flow. Moreover, GRS promoted expression of zona occludens-1 (ZO-1) and claudin-5 while inhibiting matrix metalloproteinase 2/9 (MMP-2/9) expression and myosin light chain (MLC) phosphorylation. In vitro, GRS (1, 10, and 100 ng/mL) enhanced the viability of bEnd.3 cells subjected to oxygen glucose deprivation/reoxygenation (OGD/R) and decreased sodium fluorescein permeability.
Consistent with in vivo findings, ZO-1 and claudin-5 were significantly upregulated by GRS in bEnd.3 cells under OGD/R and MMP-2/9 levels and MLC phosphorylation reduced through the Rho-associated coil-forming protein kinase (ROCK)/cofilin signaling pathway. Based on the collective findings, we propose that the TCM compound, GRS, plays a protective role against I/R-induced BBB dysfunction.
中药（TCM）为缺血性中风（一种与衰老相关的血管疾病）的治疗提供了独特的优势。生脉散（GRS）由三种活性成分组成，即人参皂苷 Rb1、鲁斯可苷元和五味子甲素，比例为 6:0.75:6。本研究的主要目的是评估 GRS 在大脑中动脉闭塞/再灌注（MCAO/R）条件下对血脑屏障（BBB）功能障碍的影响。
采用 C57BL/6J 小鼠 MCAO/R 模型，评估不同剂量 GRS（6.4、12.8 和 19.2mg/kg）对 BBB 功能障碍的保护作用。
GRS 降低了脑梗死体积和脑组织损伤程度，改善了行为评分，降低了水含量和 BBB 通透性，恢复了脑血流。此外，GRS 促进了紧密连接蛋白-1（ZO-1）和闭合蛋白-5 的表达，同时抑制了基质金属蛋白酶 2/9（MMP-2/9）的表达和肌球蛋白轻链（MLC）的磷酸化。体外实验中，GRS（1、10 和 100ng/mL）增强了氧葡萄糖剥夺/复氧（OGD/R）处理的 bEnd.3 细胞活力，降低了钠离子荧光素通透性。
与体内研究结果一致，GRS 在 OGD/R 下显著上调 bEnd.3 细胞中的 ZO-1 和闭合蛋白-5，同时通过 Rho 相关卷曲螺旋形成蛋白激酶（ROCK）/丝切蛋白信号通路降低 MMP-2/9 水平和 MLC 磷酸化。基于这些发现，我们提出中药复方 GRS 对 I/R 诱导的 BBB 功能障碍具有保护作用。
