Analysis of glomerular lesions in an experimental model induced by apolipoprotein E gene.

(1)载脂蛋白B（apoE）缺陷小鼠的病毒介导的转导：我们将含有apoE-仙台的重组腺病毒注射到apoE缺陷小鼠中，产生脂蛋白肾小球病（LPG）模型，并研究脂蛋白谱和病理学发现。我们通过分别注射含有apoE 2、3和4的腺病毒制备对照组。(2)血浆生化分析：通过含有apoE的载体，apoE被表达，并且总胆固醇（TC）和LDL水平被标准化。ApoE仙台给药小鼠表现出暂时性高血脂和TC和LDL改善不足。特别是在毛细管等速电泳中形成峰并与氧化的LDL一致的负电性LDL是显著的。因此，推测氧化LDL在LPG中起病理作用。(3)病理结果：病理结果进行了调查苏丹III染色的锇固定标本，以及通过光学显微镜和电子显微镜。在给予apoE-仙台的一些小鼠中，在系膜旁区域和血管极周围发现脂蛋白的脂蛋白积聚。这些结果表明，肾小球病变类似于LPG在人类。(4)apoE和FcRγ链缺陷小鼠的分析：有报道FcRγ链缺陷小鼠的GVH病表现为与LPG相似的含有apoE的脂蛋白血栓。本研究拟通过构建携带apoE基因的腺病毒载体，培育apoE和FcRγ链双缺陷小鼠，研究LPG的发病机制。

(1) Virus-mediated transduction of apolipoprotein B (apoE) in apoE-deficient mice : We injected recombinant adenoviruses containing apoE-Sendai into apoE-deficient mice, produced a model of lipoprotein glomerulopathy (LPG) and studied lipoprotein profiles and pathological findings. We prepared control groups by the injections of adenoviruses containing apoE2, 3 and 4, respectively.(2) Biochemical analysis in plasma : By the apoE-contained vectors, apoEs were expressed and the levels of total cholesterol (TC) and LDL were normalized. ApoE-Sendai-administered mice showed temporary hypertriglyceridemia and insufficient ameliorations of TC and LDL. Particularly, electronegative LDL, which formed a peak in capillary isotachoelectroporesis and consisted with oxidized-LDL, is marked. Accordingly, it is presumed that oxidized LDL plays a pathological role in LPG.(3) Pathological findings : Pathological findings were investigated by Sudan III stain on osmium-fixed specimens as well as by light microscopy and electron microscopy. In some mice given apoE-Sendai, lipoprotein accumulation of lipoproteins was found in the paramesangial area and around the vascular pole. These findings showed that the glomerular lesions mimicked those of LPG in human.(4) Analysis of apoE and FcRγ-chain deficient mice : It is reported that GVH disease in FcRγ-chain deficient mice shows lipoprotein thrombi containing apoE similar with those of LPG. We will try to breed apoE and FcRγ-chain double deficient mice and study the pathogenesis of LPG by the administration of adenovirus vectors containing apoE genes into the double deficient mice.