【作者】 王黎；

【导师】 吴满平；

【作者基本信息】 复旦大学 ， 生物化学与分子生物学， 2009， 博士

【摘要】 尽管高密度脂蛋白(HDL)的抗炎作用已被广泛接受,但载脂蛋白A-I(ApoA-I)的抗炎作用却了解甚少。本论文在以往研究的基础上,更深入地探讨了ApoA-I的抗炎机制,特别是ApoA-I对于单核细胞与内皮细胞的相互作用、对内毒素(LPS)诱导全身性炎症兔血浆HDL炎症指数的影响。结果显示,ApoA-I能显著减少LPS诱导的THP-1细胞释放单核细胞趋化因子-1(MCP-1)、降低oxLDL诱导的THP-1细胞迁移率(均为P＜0.01);ApoA-I显著降低LPS诱导的THP-1细胞释放可溶性白细胞选择素(sL-Selectin)、可溶性细胞间粘附分子-1(sICAM-1)、可溶性血管细胞粘附分子-1(sVCAM-1)(分别为P＜0.01,P＜0.01,P＜0.05);ApoA-I显著抑制LPS诱导的THP-1细胞表面CD11b和VCAM-1的表达(分别为P＜0.01,P＜0.05);ApoA-I能减少LPS诱导的THP-1细胞膜CD14(mCD14)的表达(P＜0.01),抑制NFκB的核内转位;单次注射ApoA-I能降低LPS诱导的全身性炎症兔血浆HDL的炎症指数,改善HDL的抗炎功能。结论:ApoA-I能抑制THP-1细胞趋化、粘附、激活,改善血浆HDL炎症指数,发挥抗炎作用。更多还原

【Abstract】 Whereas the antiinflammatory effects of high density lipoprotein(HDL) are well described,such effects of Apolipoprotein A-I(ApoA-I) are less studied.On the basis of our previous study,we furtherly explored the mechanism of antiinflammatory effects of ApoA-I,and focused especially on the interaction between monocyte and endothelial cells and plasma HDL inflammatory index in LPS-challenged rabbits.The results showed that ApoA-I significantly decreased LPS-induced MCP-1 release of THP-1 cells and oxLDL-induced THP-1 migration ratio(P＜0.01 respectively). ApoA-I significantly decreased sL-selectin,slCAM-1 and sVCAM-1 release of LPS-stimulated THP-1 cells(P＜0.01,P＜0.01,P＜0.05 respectively).Furthermore, ApoA-I significantly inhibited LPS-induced CD11b and VCAM-1 expressions on THP-1 cells(P＜0.01,P＜0.05 respectively).ApoA-I diminished LPS-induced mCD14 expression(P＜0.01) and NFκB nuclear translocation in THP-1 cells.After single dosage treatment of ApoA-I,the value of plasma HDL inflammatory index in LPS-challenged rabbits was improved significantly(P＜0.05).Conclusions:ApoA-I can inhibit the chemotaxis,adhesion and activation of THP-1 cells and impove plasma HDL inflammatory index with presenting beneficial antiinflammatory effects.更多还原