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

(1)载脂蛋白B （apoE）在apoE缺陷小鼠体内的病毒介导转导：我们将含有载脂蛋白e - sendai的重组腺病毒注射到apoE缺陷小鼠体内，建立了脂蛋白肾小球病（LPG）模型，研究了脂蛋白谱和病理结果。分别注射含apoE2、3和4的腺病毒制备对照组。(2)血浆生化分析：通过载脂蛋白e载体表达载脂蛋白e，并将总胆固醇（TC）和低密度脂蛋白（LDL）水平归一化。apoe - sendai给药小鼠出现暂时性高甘油三酯血症，TC和LDL改善不足。特别是电负性LDL，在毛细管等电电泳中形成一个峰，与氧化LDL组成。因此，假定氧化LDL在LPG中起病理作用。(3)病理表现：锇固定标本苏丹ⅲ染色及光镜、电镜观察病理表现。在给药apoE-Sendai的一些小鼠中，在脉管旁区和血管极周围发现脂蛋白积累。这些发现表明肾小球病变与人类LPG相似。(4) apoE和fcr γ链缺陷小鼠分析：有报道称，fcr γ链缺陷小鼠GVH病中出现与LPG相似的含apoE的脂蛋白血栓。我们将尝试培育apoE和fcr γ链双缺陷小鼠，并通过含apoE基因的腺病毒载体转染双缺陷小鼠，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.