首页> 外文期刊>Journal of stroke and cerebrovascular diseases: The official journal of National Stroke Association >Chinese medicine Tongxinluo capsule protects against blood-brain barrier disruption after ischemic stroke by inhibiting the low-density lipoprotein receptor-related protein 1 pathway in mice
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Chinese medicine Tongxinluo capsule protects against blood-brain barrier disruption after ischemic stroke by inhibiting the low-density lipoprotein receptor-related protein 1 pathway in mice

机译:中医通过抑制小鼠抑制低密度脂蛋白受体相关蛋白1途径,防止缺血性中风后血脑屏障中断

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Background: Chinese medicine Tongxinluo capsule (TXL) has been extensively used to treat ischemic stroke in China, and one of its mechanisms is to protect against blood brain barrier (BBB) disruption after stroke. However, the underlying protective mechanisms are not fully illuminated. It is reported that the low-density lipoprotein receptor-related protein 1 (LRP-1) is involved in BBB disruption after brain ischemia. In this study, we explored whether TXL could downregulate LRP-1 expression and subsequently protect against BBB disruption after stroke using permanent middle cerebral artery occlusion (pMCAO) in mice. Methods: The animal model of ischemic stroke was induced by pMCAO in male adult C57BL/6J mice. The mice were orally administered TXL (3.0 g/kg) at 1, 3 and 21 h after pMCAO. Meanwhile, the LRP-1 antagonist receptor associated protein (RAP) was intracerebroventricularly injected at 1 and 21 h after stroke. We measured the following parameters at 6 and 24 h: LRP-1 protein level, BBB leakage, and the expression of tight junction (TJ) proteins including occludin, claudin-5 and zonula occludens-1 (ZO-1). Results: Our results showed that TXL downregulated LRP-1 level, upregulated these TJ proteins level, and reduced BBB leakage in peri-infarct regions after pMCAO. Further study found that the inhibitor RAP played the same role as did TXL in upregulating these TJ proteins level and reducing BBB leakage after stroke. Conclusion: Our study demonstrates that TXL protects against BBB disruption after stroke via inhibiting the LRP-1 pathway.
机译:背景:中药通心络胶囊(TXL)在中国已被广泛用于治疗缺血性中风,其机制之一是预防中风后血脑屏障(BBB)的破坏。然而,潜在的保护机制尚未完全阐明。据报道,低密度脂蛋白受体相关蛋白1(LRP-1)参与脑缺血后BBB的破坏。在这项研究中,我们使用永久性大脑中动脉阻塞(pMCAO)在小鼠中探索通心络是否能下调LRP-1的表达,从而保护脑卒中后BBB的破坏。方法:用pMCAO在雄性成年C57BL/6J小鼠上建立缺血性脑卒中动物模型。小鼠在pMCAO后1、3和21小时口服TXL(3.0 g/kg)。同时,在卒中后1小时和21小时侧脑室注射LRP-1拮抗剂受体相关蛋白(RAP)。我们在6小时和24小时测量了以下参数:LRP-1蛋白水平、BBB渗漏和紧密连接(TJ)蛋白的表达,包括闭塞素、克劳丁-5和闭塞带-1(ZO-1)。结果:我们的研究结果显示,通心络能下调LRP-1水平,上调这些TJ蛋白水平,并减少pMCAO后梗死周围区域的BBB渗漏。进一步研究发现,抑制剂RAP在上调这些TJ蛋白水平和减少中风后BBB渗漏方面与TXL起到了相同的作用。结论:我们的研究表明通心络可通过抑制LRP-1途径保护脑卒中后BBB的破坏。

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