吡格列酮对动脉粥样硬化CD40/CD40L炎症信号通路的影响及其机制的探讨
摘要
背景：
目前认为动脉粥样硬化是一种免疫炎症性疾病。急性冠脉综合征是一个伴有斑块破裂和血栓形成的急性炎症。血小板的激活可见于动脉粥样硬化的整个过程。免疫调节因子CD40／CD40L对动脉粥样硬化的发生、进展和预后起着非常重要的作用。有报道血浆sCD40L是冠心病患者急性心血管事件的独立预测因子，急性冠脉综合征患者血浆sCD40L水平明显高于稳定性冠心病者，sCD40L主要来源于血小板。最近还有研究证实高脂血症能增加血小板、内皮细胞、单核细胞CD40／CD40L的表达及血浆sCD40L的水平。另外有研究证实阻断CD40／CD40L信号通路能明显抑制斑块的进展，稳定已形成的斑块。氧化低密度脂蛋白和CD40／CD40L共同表达于动脉粥样斑块处。PPAR-γ是核受体家族的转录调节因子，研究证实PPAR-γ配体不仅能改善代谢而且具有抗炎作用，从而能保护血管，防止动脉粥样硬化的进展。
目的：
观察不同冠心病患者中血小板CD40L水平的变化，进一步探讨急性冠脉综合征临床预测的炎性指标。观察氧化低密度脂蛋白刺激人脐静脉内皮细胞CD40／CD40L的影响，探讨吡格列酮对氧化低密度脂蛋白刺激下的人脐静脉内皮细胞CD40／CD40L表达的影响及可能机制。探讨吡格列酮对高脂饮食下兔主动脉粥样硬化病变及CD40L表达的影响。
Background:
Atherosclerosis is considered as an immuno-inflammatory disease. Acute coronary syndrome is a process of acute inflammation accompanied by plaque rupture and thrombosis.Platelet activation exists in the whole pathogenesis process of atherosclerosis.The immune modulator CD40/CD40L play an important role in the initiation 、 progression and prognosis of atherosclerosis, recently studies showed plasma sCD40L was an independent indicator of prognosis in patients with coronary heart disease .Patients with acute coronary syndrome showed higher level of sCD401 than those stable coronary heart diseases. Recently, studies demonstrated that hypercholesterolemia(HC), one of the major cardiovascular risk factors, increased CD40 and CD40L expression on platelets ,endothelial cells and monocytes as well as plasma levels of soluble CD40L. In addition, it has been shown that blocking CD40-CD40L interactions significantly prevented the development of atherosclerotic plaques and reduced already pre-established lesions. Both
目前认为动脉粥样硬化是一种免疫炎症性疾病。急性冠脉综合征是一个伴有斑块破裂和血栓形成的急性炎症。血小板的激活可见于动脉粥样硬化的整个过程。免疫调节因子CD40／CD40L对动脉粥样硬化的发生、进展和预后起着非常重要的作用。有报道血浆sCD40L是冠心病患者急性心血管事件的独立预测因子，急性冠脉综合征患者血浆sCD40L水平明显高于稳定性冠心病者，sCD40L主要来源于血小板。最近还有研究证实高脂血症能增加血小板、内皮细胞、单核细胞CD40／CD40L的表达及血浆sCD40L的水平。另外有研究证实阻断CD40／CD40L信号通路能明显抑制斑块的进展，稳定已形成的斑块。氧化低密度脂蛋白和CD40／CD40L共同表达于动脉粥样斑块处。PPAR-γ是核受体家族的转录调节因子，研究证实PPAR-γ配体不仅能改善代谢而且具有抗炎作用，从而能保护血管，防止动脉粥样硬化的进展。
目的：
观察不同冠心病患者中血小板CD40L水平的变化，进一步探讨急性冠脉综合征临床预测的炎性指标。观察氧化低密度脂蛋白刺激人脐静脉内皮细胞CD40／CD40L的影响，探讨吡格列酮对氧化低密度脂蛋白刺激下的人脐静脉内皮细胞CD40／CD40L表达的影响及可能机制。探讨吡格列酮对高脂饮食下兔主动脉粥样硬化病变及CD40L表达的影响。
Background:
Atherosclerosis is considered as an immuno-inflammatory disease. Acute coronary syndrome is a process of acute inflammation accompanied by plaque rupture and thrombosis.Platelet activation exists in the whole pathogenesis process of atherosclerosis.The immune modulator CD40/CD40L play an important role in the initiation 、 progression and prognosis of atherosclerosis, recently studies showed plasma sCD40L was an independent indicator of prognosis in patients with coronary heart disease .Patients with acute coronary syndrome showed higher level of sCD401 than those stable coronary heart diseases. Recently, studies demonstrated that hypercholesterolemia(HC), one of the major cardiovascular risk factors, increased CD40 and CD40L expression on platelets ,endothelial cells and monocytes as well as plasma levels of soluble CD40L. In addition, it has been shown that blocking CD40-CD40L interactions significantly prevented the development of atherosclerotic plaques and reduced already pre-established lesions. Both
引文
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