Traditional Chinese medicine, Xue-Fu-Zhu-Yu decoction, potentiates tissue plasminogen activator against thromboembolic stroke in rats
Traditional Chinese medicine, Xue-Fu-Zhu-Yu decoction, potentiates tissue plasminogen activator against thromboembolic stroke in rats
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DOI：
10.1016/j.jep.2011.01.033
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发表时间：
2011-04-12
影响因子：
5.4
通讯作者：
Sheu, Joen-Rong
中科院分区：
文献类型：
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作者：
Lee, Jie-Jen;Hsu, Wen-Hsien;Sheu, Joen-Rong
本研究的目的：血府逐瘀汤（XFZYD）是治疗心血管疾病的著名中药。该XFZYD的治疗效果已被充分证明，特别是在治疗动脉粥样硬化和高脂血症方面。由于该汤剂可诱导内皮祖细胞血管生成，因此可为缺血性疾病的治疗提供实验证据。因急性缺血性中风入院的患者最初被认为是重组组织纤溶酶原激活剂（rt-PA）的候选者。然而，rt-PA 治疗由于其主要的出血副作用，仍然不太理想。因此，医学研究一直致力于寻找缺血性中风的替代和/或补充疗法。在本研究中，我们评估了 XFZYD 联合或不联合 rt-PA 对血栓栓塞性中风大鼠模型的保护作用。材料和方法：使用脑血栓栓塞性中风动物模型和免疫印迹分析来评估 XFZYD 和 rt-PA 的作用。结果：单独使用 rt-PA（8 mg/kg）或 XFZYD（1.5 和 3.0 g/kg/天）治疗显示，与溶剂处理的大鼠相比，梗塞体积。然而，XFZYD（1.5 和 3.0 g/kg/天）明显增强了 rt-PA 介导的脑缺血区域梗塞体积的减少。此外，rt-PA治疗显着降低了缺血区域的肿瘤坏死因子（TNF）-α和诱导型一氧化氮合酶（iNOS）的表达，但没有降低缺氧诱导因子（HIF）-1α或活性caspase-3的表达，而XFZYD（3.0 g/kg/天）治疗显着降低了缺血区域中所有这些蛋白质的表达。此外，XFZYD（1.5 和 3.0 g/kg/天）治疗明显增强了 rt-PA 介导的 TNF-α、iNOS、HIF-1 α 和活性 caspase-3 表达的减少。 结论：本研究结果表明，XFZYD 增强了 rt-PA 介导的针对大鼠血栓栓塞性中风的神经保护作用。这种神经保护作用可能是通过抑制 HIF-1 α 和 TNF-α 介导的，然后抑制炎症反应（即 iNOS）和细胞凋亡（活性 caspase-3）。这些结果为XFZYD联合rt-PA治疗缺血性脑卒中的治疗价值的科学验证提供了更好的理解。 (C) 2011 Elsevier Ireland Ltd. 保留所有权利。
Aim of this study: The Xue-Fu-Zhu-Yu decoction (XFZYD) is a well-known traditional Chinese medicine for treating cardiovascular diseases. The therapeutic effects of this XFZYD have been well documented especially in treating of atherosclerosis and hyperlipidemia. Since this decoction can induce endothelial progenitor cell angiogenesis, it can provide experimental evidence for the treatment of ischemic diseases. Patients who are admitted to the hospital with acute ischemic stroke are initially considered candidates for the recombinant tissue plasminogen activator (rt-PA). However, rt-PA therapy is still lesser than ideal due to its major side effect of hemorrhaging. Therefore, medical research has been devoted to finding an alternative and/or complementary therapy for ischemic stroke. In the present study, we evaluated the protective effect of the combination of XFZYD with or without rt-PA in a rat model of thromboembolic stroke.Materials and methods: A cerebral thromboembolic stroke animal model and immunoblotting analysis were used to assess the effects of XFZYD and rt-PA.Results: Treatment with rt-PA (8 mg/kg) or XFZYD (1.5 and 3.0 g/kg/day) alone showed slight reductions in the infarct volume compared to solvent-treated rats. However, XFZYD (1.5 and 3.0 g/kg/day) obviously potentiated rt-PA-mediated reduction in the infarct volume in cerebral ischemic regions. In addition, treatment with rt-PA significantly reduced both tumor necrosis factor (TNF)-alpha and inducible nitric oxide synthase (iNOS) but not hypoxia-inducible factor (HIF)-1 alpha or active caspase-3 expressions in ischemic regions, whereas treatment with XFZYD (3.0 g/kg/day) significantly reduced all of these protein expressions in ischemic regions. Moreover, treatment with XFZYD (1.5 and 3.0 g/kg/day) obviously potentiated rt-PA-mediated reductions in TNF-alpha, iNOS, HIF-1 alpha, and active caspase-3 expressions.Conclusions: Results of this study suggest that XFZYD potentiated rt-PA-mediated neuroprotection against thromboembolic stroke in rats. This neuroprotection is probably mediated by the inhibition of HIF-1 alpha and TNF-alpha, followed by the inhibition of inflammatory responses (i.e., iNOS) and apoptosis (active caspase-3). These results provide a better understanding of the scientific validation of the therapeutic value of the combination of XFZYD with rt-PA in ischemic stroke. (C) 2011 Elsevier Ireland Ltd. All rights reserved.