Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing 100191, China; The Key Discipline for Basic Integration of Chinese and Western Medicine (microcirculation) of the National Administration of Traditional Chinese Medicine, Beijing 100191, China.
Department of Traditional Chinese Medicine, Peking University Third Hospital, Beijing 100191, China.
J Ethnopharmacol. 2024 Jan 10;318(Pt B):117024. doi: 10.1016/j.jep.2023.117024. Epub 2023 Aug 11.
YangXueQingNaoWan (YXQNW), a compound Chinese medicine, has been widely used for dizziness, irritability, insomnia, and dreaminess caused by blood deficiency and liver hyperactivity in China. However, whether YXQNW can inhibit cerebral microvascular exudation and cerebral hemorrhage (CH) caused by blood brain barrier (BBB) damage after tissue plasminogen activator (tPA) still unknown.
To observe the effect of YXQNW on cerebral microvascular exudation and CH after tPA and investigate its mechanism in protecting BBB.
Male C57BL/6 N mice suffered from ischemia stroke by mechanical detachment of carotid artery thrombi with the stimulation of ferric chloride. Then mice were treated with tPA (10 mg/kg) and/or YXQNW (0.72 g/kg) at 4.5 h. Cerebral blood flow (CBF), infarct size, survival rate, neurological scores, gait analysis, Evans blue extravasation, cerebral water content, fluorescein isothiocyanate-labeled albumin leakage, hemorrhage, junction and basement membrane proteins expression, leukocyte adhesion and matrix metalloproteinases (MMPs) expression were evaluated 24 h after tPA. Proteomics was used to identify target proteins.
YXQNW inhibited cerebral infarction, neurobehavioral deficits, decreased survival, Evans blue leakage, albumin leakage, cerebral water content and CH after tPA thrombolysis; improved CBF, low-expression and degradation of junction proteins, basement membrane proteins, Arhgap21 and its downstream α-catenin and β-catenin proteins expression; and suppressed the increase of adherent leukocytes and the release of MMP-9 derived from macrophage.
YXQNW relieved BBB damage and attenuated cerebral microvascular exudation and CH after tPA thrombolysis. The effect of YXQNW on cerebral microvascular exudation was associated with the inhibition of the low-expression of junction proteins, especially AJs mediated by Rho GTPase-activating protein 21 (Arhgap21), while the effect on CH was associated with the inhibition of leukocyte adhesion, the release of MMP-9 derived from macrophage, and low-expression and degradation of collagen IV and laminin in the vascular basement membrane.
养血清脑丸（YXQNW）是一种复方中药，在中国广泛用于治疗血虚肝旺引起的头晕、烦躁、失眠、多梦。然而，YXQNW 是否能抑制组织型纤溶酶原激活物（tPA）后血脑屏障（BBB）损伤引起的脑微血管渗出和脑出血（CH）尚不清楚。
观察 YXQNW 对 tPA 后脑微血管渗出和 CH 的影响，并探讨其保护 BBB 的机制。
雄性 C57BL/6N 小鼠通过机械分离颈总动脉血栓并用氯化铁刺激引起缺血性脑卒中。然后在 4.5h 时用 tPA（10mg/kg）和/或 YXQNW（0.72g/kg）处理小鼠。在 tPA 后 24h 评估脑血流量（CBF）、梗死面积、存活率、神经评分、步态分析、伊文思蓝外渗、脑水含量、荧光素异硫氰酸酯标记白蛋白渗漏、出血、连接和基底膜蛋白表达、白细胞黏附和基质金属蛋白酶（MMPs）表达。蛋白质组学用于鉴定靶蛋白。
YXQNW 抑制 tPA 溶栓后脑梗死、神经行为缺陷、存活率降低、伊文思蓝渗漏、白蛋白渗漏、脑水含量和 CH；改善 CBF、连接蛋白和基底膜蛋白、Arhgap21 及其下游α-连环蛋白和β-连环蛋白蛋白表达的低表达和降解；并抑制巨噬细胞来源的 MMP-9 释放和黏附白细胞的增加。
YXQNW 减轻了 tPA 溶栓后 BBB 损伤，减轻了脑微血管渗出和 CH。YXQNW 对脑微血管渗出的作用与 Rho GTPase 激活蛋白 21（Arhgap21）介导的连接蛋白，尤其是 AJs 的低表达抑制有关，而对 CH 的作用与白细胞黏附抑制、巨噬细胞来源的 MMP-9 释放以及血管基底膜中胶原 IV 和层粘连蛋白的低表达和降解有关。
