Liu Shen, Wei Cong, Kang Ning, He Qilong, Liang Junqing, Wang Hongtao, Chang Liping, Chen Daohong, Zhang Qiuyan, Chang Chengcheng, Zhang Junfang, Ren Hong, Wu Yiling
Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.
National Key Laboratory of Collateral Disease Research and Innovative Chinese Medicine, Hebei Yiling Chinese Medicine Research Institute, Shijiazhuang, China.
Microcirculation. 2018 Feb;25(2). doi: 10.1111/micc.12437.
The aim of this study was to examine the effect of TXL, a Chinese medicine prescription, on cerebral microcirculatory disturbances after pMCAO in mice using TPLSM and further explore the underlying mechanisms.
Adlut male C57BL/6J mice were subjected to pMCAO and orally administered with TXL (3.0, 1.5 and 0.75 g/kg/d) at 1, 3, and 21 hours after pMCAO. The following parameters were examined at 6 and 24 hours after pMCAO: neurological deficits, infarct volume, BBB permeability, cerebral microvessel structure, brain microcirculation (TPLSM imaging), vasoactive factors, and adhesion molecules.
TXL improved neurological deficits, reduced infarct volume, attenuated BBB disruption, protected cerebral microvessel structure, increased cerebral capillary flow velocity and volume flux, and inhibited leukocyte-endothelial cell interactions at 6 or 24 hours after pMCAO. The therapeutic efficacy was exerted in a dose-dependent manner. Further study revealed that TXL (high dose) regulated the expression of PGI2, TXA2, and ET-1, and suppressed ICAM-1 and P-selectin.
TXL alleviates cerebral microcirculatory disturbances against ischemic injury by modulating endothelial function and inhibiting leukocyte-endothelial cell interactions. These effects are associated with regulating the expression of PGI2, TXA2, and ET-1, and suppressing ICAM-1 and P-selectin expression.
本研究旨在运用双光子激光扫描显微镜（TPLSM）检测中药方剂通心络（TXL）对小鼠大脑中动脉闭塞（pMCAO）后脑微循环障碍的影响，并进一步探究其潜在机制。
成年雄性C57BL/6J小鼠接受pMCAO手术，并于pMCAO术后1、3和21小时口服给予TXL（3.0、1.5和0.75克/千克/天）。在pMCAO术后6和24小时检测以下参数：神经功能缺损、梗死体积、血脑屏障（BBB）通透性、脑微血管结构、脑微循环（TPLSM成像）、血管活性因子和黏附分子。
TXL改善了神经功能缺损，减小了梗死体积，减轻了BBB破坏，保护了脑微血管结构，增加了脑毛细血管流速和容积通量，并在pMCAO术后6或24小时抑制了白细胞与内皮细胞的相互作用。治疗效果呈剂量依赖性。进一步研究表明，TXL（高剂量）调节了前列环素（PGI2）、血栓素A2（TXA2）和内皮素-1（ET-1）的表达，并抑制了细胞间黏附分子-1（ICAM-1）和P-选择素。
TXL通过调节内皮功能和抑制白细胞与内皮细胞的相互作用来减轻脑微循环障碍对缺血性损伤的影响。这些作用与调节PGI2、TXA2和ET-1的表达以及抑制ICAM-1和P-选择素的表达有关。
