【作者】 王小清；

【导师】 赵水平；

【作者基本信息】 中南大学 ， 内科学， 2003， 博士

【摘要】 背景：越来越多的实验及临床研究表明肥胖与心血管疾病存在着密切的关系。肥胖是由于脂肪组织的过量聚集，研究认为脂肪组织可分泌多种炎症介质，参与了动脉粥样硬化的发生和发展，但对其作用机制认识尚很肤浅。内皮功能受损是动脉粥样硬化发展的起始步骤，目前脂肪组织对内皮功能的损伤的研究甚少。他汀类药物调脂外抗炎机理的作用近年来研究越来越受到人们的重视。因此，对脂肪分泌物进行分析，研究其培养液对内皮的直接或间接作用，并采取适当的干预措施对于肥胖与动脉粥样硬化的关系的认识及防治动脉粥样硬化将有着重要的意义。 目的：探讨肥胖致动脉粥样硬化的炎症机理。 方法：观察脂肪组织分泌IL-6及PAI-1的情况，脂肪组织培养液对内皮细胞ICAM-1表达及分泌的影响及对肝细胞分泌CRP的影响，CRP对内皮细胞的作用，并采取阿托伐他汀等药物进行干预。 结果：1．脂肪组织可分泌IL-6及PAI-1等物质，且内脏脂肪分泌量高于皮下脂肪；内脏及皮下脂肪分泌IL-6与BMI呈正相关（r分别为0.85、0.69，P均＜0.01），分泌PAI-1与BMI也呈正相关（r分别为0.63、0.71，P均＜0.01）。 2．内脏脂肪培养液刺激HepG₂分泌CRP作用强于皮下脂肪培养液。 3．CRP可刺激HUVEC分泌sICAM-1，且呈剂量依赖性。 4．脂肪组织培养液引起HUVEC分泌及表达ICAM-1增加，且内脏脂肪强于皮下脂肪。 5．阿托伐他汀可通过脂肪组织及内皮细胞抑制炎症介质的分泌及表达。 结论： 1．脂肪组织可分泌炎症介质。 2．脂肪组织分泌物作用于内皮细胞产生炎性介质。 3．脂肪组织分泌物可刺激肝细胞产生CRP，CRP能损伤内皮功能。 4．内脏脂肪致炎作用强于皮下脂肪。 5．阿托伐他汀可抑制炎症介质的分泌及表达，具有抗炎作用。更多还原

【Abstract】 Background: Increasing experiments and clinical studies show that obesity is associated with cardiovascular disease. Obesity is accumulation of excess adipose tissue. Studies show that adipose tissue secreting many kinds of inflammatory mediator plays a important role in onset and development of atherosclerosis, but the mechanism is unclear. Th injury of endothelium function is the earliest steps in atherogenesis. There is less reports about injury of adipose tissue on endothelium. In recent years more and more studies accumulate on that statins have anti-inflammatory properties independent of their cholesterol-lowering effects. For what is said above, we analyse the components of the adipose tissue cultured media and detect the direct or indirect effect of the media on endothelium, then intervene with some drugs. It will be very important to knew the association between obesity and atherosclerosis and to prevent from atherosclerosis.Objectives: To detect the inflammatory mechanism of atherosclerosis induced by obesity.Methods: To exam IL-6 and PAI-1 level releasing from adipose tissue. To detect expression of intercellular adhesion molecular (ICAM-1) in protein level and mRNA level of material released from dipose tissue on endothelial cells and the effect of adipose tissue on HepG2 and that CRP on endothelial cells, than intervene with drugs such as atorvastatin.Results: 1. IL-6 and PAI-1 level released from omental adipose tissue are higher than that from subcutaneous fat. IL-6 level secreted from omental and subcutaneous fat is correlated with BMI (r=0.85, 0.69, P<0.01, respectively), PAI-1 level released from that is associated with BMI, too (r=0.63, 0.71, all P<0.01).2. The effect of CRP released from HepG2 stimulated with omental fat conditioned media is stronger than that stimulated with subcutaneous fat conditioned media.3. sICAM-1 releasing from HUVEC stimulated with CRP is dose-dependent.4. Expression of ICAM-1 in protein and mRNA level of adipose tissue on endothelial cells is stronger than control. The effect of omental adipose tissue culturedmeelia is stronger than that of subcutaneous.5. Atorvastatin can suppress the expression and release of inflammatory mediator by adipose tissue and endothelial cells.Conclusion: 1. adipose tissue can release inflammatory mediator.2. Substance receased from adipose tissue can induce endothelial cells producing inflammatory mediator.3. CRP released from HepGa stimulated with adipose tissue cultured media and CRP damaged endothelial function.4. inflammation induced by omental adipose tissue is stronger than that by subcutaneous adipose tissue.5. Atrovastatin suppress expression of inflammatory mediator. It has an effect of anti-inflammation.更多还原