Cerebralcare Granule® attenuates blood-brain barrier disruption after middle cerebral artery occlusion in rats
Cerebralcare Granule® attenuates blood-brain barrier disruption after middle cerebral artery occlusion in rats
复制标题
DOI：
10.1016/j.expneurol.2012.07.017
复制
发表时间：
2012-10-01
影响因子：
5.3
通讯作者：
Han, Jing-Yan
中科院分区：
文献类型：
--
作者：
Huang, Ping;Zhou, Chang-Man;Han, Jing-Yan
血脑屏障（BBB）的破坏和随后的水肿是缺血性脑卒中发病的主要原因，目前的临床治疗仍然不满意。脑康颗粒（R）（CG）是一种在我国广泛应用的治疗脑血管疾病的复方中药。CG对全脑缺血后脑微循环障碍和海马神经元损伤有明显的保护作用。然而，CG对脑缺血后BBB破坏的影响尚未研究。在这项研究中，我们研究了CG对局灶性脑缺血/再灌注（I/R）大鼠模型的BBB破坏的治疗作用。对雄性Sprague-Dawley大鼠（250至300 g）进行1 h大脑中动脉闭塞（MCAO）。再灌注后3 h开始灌胃CG（0.4g/kg或0.8g/kg），以后每天1次，连续6天。结果表明，模型组大鼠伊文思蓝外渗、脑含水量、白蛋白漏出、梗死体积和神经功能缺损均明显增加，CG治疗组明显减轻。T2加权MRI和电子显微镜进一步证实了CC治疗大鼠脑水肿的减轻。CG治疗可改善脑血流量（CBF）。蛋白质印迹分析和共聚焦显微镜显示紧密连接蛋白claudin-5。缺血后，内皮细胞间的JAM-1、occludin和zonulaoccluden-1明显降解，而内皮细胞小窝的主要标志物caveolin-1蛋白表达增加，CG处理后，上述变化均得到缓解。结论：CG后处理可显著降低BBB通透性和脑水肿，其机制可能与抑制内皮细胞紧密连接蛋白降解和caveolin-1表达有关。这些发现为缺血性卒中的治疗提供了一种新的方法。(C)2012 Elsevier Inc. All rights reserved.
Disruption of blood-brain barrier (BBB) and subsequent edema are major contributors to the pathogenesis of ischemic stroke, for which the current clinical therapy remains unsatisfied. Cerebralcare Granule (R) (CG) is a compound Chinese medicine widely used in China for treatment of cerebrovascular diseases. CG has been demonstrated efficacy in attenuating the cerebral microcirculatory disturbance and hippocampal neuron injury following global cerebral ischemia. However, the effects of CG on BBB disruption following cerebral ischemia have not been investigated. In this study, we examined the therapeutic effect of CG on the BBB disruption in a focal cerebral ischemia/reperfusion (I/R) rat model. Male Sprague-Dawley rats (250 to 300 g) were subjected to 1 h middle cerebral artery occlusion (MCAO). CG (0.4 g/kg or 0.8 g/kg) was administrated orally 3 h after reperfusion for the first time and then once daily up to 6 days. The results showed that Evans blue extravasation, brain water content, albumin leakage, infarction volume and neurological deficits increased in MCAO model rats, and were attenuated significantly by CG treatment. T2-weighted MRI and electron microscopy further confirmed the brain edema reduction in CC-treated rats. Treatment with CG improved cerebral blood flow (CBF). Western blot analysis and confocal microscopy showed that the tight junction proteins claudin-5. JAM-1, occludin and zonula occluden-1 between endothelial cells were significantly degradated, but the protein expression of caveolin-1, the principal marker of caveolae in endothelial cells, increased after ischemia, all of which were alleviated by CG treatment. In conclusion, the post-treatment with CG significantly reduced BBB permeability and brain edema, which were correlated with preventing the degradation of the tight junction proteins and inhibiting the expression of caveolin-1 in the endothelial cells. These findings provide a novel approach to the treatment of ischemic stroke. (C) 2012 Elsevier Inc. All rights reserved.