载脂蛋白E-基因敲除鼠VLDL和IDL在动脉硬化中的作用

THE ROLE OF VERY LOW AND INTERMEDIATE DENSITY LIPOPROTEIN FRACTION ISOLATED FROM APOLIPOPROTEIN E KNOCKOUT MICE IN ATHEROSCLEROSIS

探讨载脂蛋白Ｅ（ａｐｏＥ）－基因敲除鼠极低密度脂蛋白（ＶＬＤＬ）和中间密度脂蛋白（ＩＤＬ）组分（ａｐｏＥｋｏ－ＶＬＤＬ／ＩＤＬ）致动脉硬化作用．采用超离法从ａｐｏＥ－基因敲除鼠血浆中分离ＶＬＤＬ和ＩＤＬ组分，与鼠腹腔巨噬细胞共育，观察ａｐｏＥｋｏ－ＶＬＤＬ／ＩＤＬ与巨噬细胞的相互作用．ＡｐｏＥｋｏ－ＶＬＤＬ／ＩＤＬ导致细胞胆固醇酯含量显著增加．其诱导的细胞［３Ｈ］胆固醇油酸脂量高达１５．１ｎｍｏｌ／ｍｇ细胞蛋白，是天然低密度脂蛋白的８．４倍．形态学观察显示，经ａｐｏＥｋｏ－ＶＬＤＬ／ＩＤＬ处理的巨噬细胞与苏丹黑Ｂ呈阳性染色．细胞结合实验表明，１２５Ｉ－ａｐｏＥｋｏ－ＶＬＤＬ／ＩＤＬ与巨噬细胞的总结合可被非标记配基取代８０％以上，特异结合呈一饱和图形．同时细胞缔合和细胞内降解实验也显示相似结果．

To inversitgate the atherogenic role of VLDL and IDL isolated from plasma of apoE knockout mice. The lipoprotein fraction containing both VLDL and IDL (apoEko VLDL/IDL) was isolated from plasma of apoE knockout mice by ultracentrifugation and its interaction with peritoneal macrophages obtained from apoE knockout mice was studied. ApoEko VLDL/IDL resulted in significant increase in cellular CE content. Morphologically, after exposure to apoEko VLDL/IDL, macrophages became strongly stained with Sudan black B. The total binding of 125 I apoEko VLDL/IDL to macrophages was effectively replaced by over 80% by an excess unlabeled ligand. Specific binding exhibited a saturation pattern. Similar results were obtained with cell association and degradation experiments. ApoEko VLDL/IDL in its unmodified form produce significant CE accumulation in macrophages through a specific and apoE independent pathway.