载脂蛋白A-I抑制THP-1细胞趋化、粘附、激活及对HDL炎症指数的改善作用

发布时间：2018-05-03 07:04

本文选题：人载脂蛋A-I(ApoA-I) + THP-1细胞　；参考：《复旦大学》2009年博士论文

【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。
[Abstract]:Although the anti-inflammatory effects of HDL) have been widely accepted, little is known about the anti-inflammatory effects of apolipoprotein A-Ig ApoA-I. On the basis of previous studies, the mechanism of anti-inflammation of ApoA-I, especially the effect of ApoA-I on the interaction between monocytes and endothelial cells, and on the plasma HDL inflammation index induced by endotoxin in rabbits were discussed. The results showed that ApoA-I could significantly reduce the release of monocyte chemokine, MCP-1, and the mobility of THP-1 cells induced by oxLDL (all P < 0.01). ApoA-I could significantly reduce the release of soluble leukocyte selectin (SL-Selectinine), soluble leukocyte selectin (SL-Selectinine) from THP-1 cells induced by LPS. The expression of CD11b and VCAM-1 on the surface of THP-1 cells induced by LPS (P < 0.01, P < 0.01, P < 0.05, respectively) was significantly inhibited by the intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, and soluble vascular cell adhesion molecule-1 (P < 0.01, P < 0.01, respectively), and the nuclear translocation of NF 魏 B was inhibited by ApoA-I (P < 0.01, P < 0.05, respectively), while the expression of CD14mCD14 on THP-1 cell membrane induced by LPS was decreased (P < 0.01), and the nuclear translocation of NF 魏 B was inhibited by ApoA-I (P < 0.01, P < 0.01, respectively). Single injection of ApoA-I could decrease the inflammatory index of plasma HDL and improve the anti-inflammatory function of HDL in rabbits with systemic inflammation induced by LPS. Conclusion: ApoA-I can inhibit the chemotaxis, adhesion and activation of THP-1 cells, improve the inflammatory index of plasma HDL, and play an anti-inflammatory effect.
【学位授予单位】：复旦大学
【学位级别】：博士
【学位授予年份】：2009
【分类号】：R363

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