Lipoprotein glomerulopathy induced by ApoE-Sendai is different from glomerular lesions in aged apoE-deficient mice
Lipoprotein glomerulopathy induced by ApoE-Sendai is different from glomerular lesions in aged apoE-deficient mice
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DOI：
10.1007/s10157-009-0195-1
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发表时间：
2009-10-01
影响因子：
2.3
通讯作者：
Saito, Takao
中科院分区：
文献类型：
--
作者：
Ishimura, Atsunori;Watanabe, Maho;Saito, Takao
载脂蛋白（apoE）突变体apoE - sendai （Arg145Pro）是人类脂蛋白肾小球病（LPG）的主要致病因素之一。引入apoE- sendai基因的apoE缺陷小鼠（apoE - sendai小鼠）产生了小鼠LPG对应体，而apoE缺陷小鼠（apoE KO小鼠）也有报道，无论引入apoE- sendai基因，都会自发发生LPG样病变。在本研究中，我们通过详细的组织学和脂蛋白谱分析来区分这两种模型的肾脏病变，并阐明apoE变异的作用。采用腺病毒载体注射诱导apoe -仙台小鼠。对apoE-仙台小鼠和apoE- KO小鼠肾脏的lpg样病变进行组织病理学评价。同时检测了两种小鼠的血浆脂质和脂蛋白。光镜下观察ApoE-Sendai小鼠肾脏组织学改变（50只小鼠中有40只，轻度24只，中度13只，重度3只）。特征性病变是扩张的血管腔，模拟人液化石油气的脂蛋白血栓。在老年apoE KO小鼠苏木精-伊红染色切片中发现了类似的变化。同时，周期酸- schiff、Azan Mallory和Oil red O/Sudan III染色切片显示apoE - sendai小鼠扩张的管腔中主要含有脂质和脂蛋白，而老年apoE KO小鼠扩张的管腔中含有更多其他物质，如蛋白质和原纤维。这些发现得到了电子显微照片的支持，在apoE - sendai小鼠中观察到圆形液滴，表明脂蛋白存在，但在老年apoE - KO小鼠中没有。在apoE KO小鼠肾脏中检测到大量抗小鼠CD68 Ab阳性细胞。这与ApoE-Sendai小鼠的结果形成对比。两类小鼠血浆脂蛋白组成完全不同。老年apoE KO小鼠肾脏确实出现了形态改变，但肾小球病变的组织学表现与apoE -仙台小鼠肾脏不同。根据组织学结果和血浆脂蛋白谱，apoE -仙台小鼠是人液化石油气的小鼠模型，而不是apoE - KO小鼠。这意味着apoE变体对LPG至关重要。
A mutant of apolipoproteinE (apoE), ApoE-Sendai (Arg145Pro), is one of the major causative factors of human lipoprotein glomerulopathy (LPG). An apoE-deficient mouse with introduced ApoE-Sendai gene (ApoE-Sendai mouse) developed a murine counterpart of LPG, whereas it was also reported that apoE-deficient mouse (apoE KO mouse) spontaneously developed LPG-like lesion regardless of introduction of ApoE-Sendai gene. In the present study, we differentiated renal lesions between these two models by detailed analyses of histology and lipoprotein profile, and clarified the role of apoE variants.ApoE-Sendai mice were induced by injection of adenovirus vectors. The kidneys showing LPG-like lesions in apoE-Sendai and apoE KO mice were histopathologically evaluated. Plasma lipids and lipoproteins of both mice were also examined.Histological alteration of the kidney in ApoE-Sendai mice was observed with light microscopy (in 40 out of 50 mice; mild 24, moderate 13, severe 3). Characteristic lesions were dilated vascular lumens mimicking lipoprotein thrombi in human LPG. Similar changes were found in hematoxylin-eosin stained sections of aged apoE KO mice. Meanwhile, periodic acid-Schiff, Azan Mallory, and Oil red O/Sudan III stained sections revealed that the dilated lumens of ApoE-Sendai mice mainly contained lipids and lipoproteins but those of aged apoE KO mice contained much other materials, e.g., proteins and fibrils. These findings were supported by electron micrographs, in which round-shaped droplets indicating lipoproteins were observed in ApoE-Sendai mice but not in aged apoE KO mice. In the kidney of apoE KO mice many anti-mouse CD68 Ab positive cells were detected. This contrasts with the result seen in ApoE-Sendai mice. The plasma lipoprotein compositions of the two types of mice were totally different.It was certain that the kidneys of aged apoE KO mice showed morphological alteration, but the histological findings of glomerular lesions were different from those seen in the kidneys of ApoE-Sendai mice. According to the histological findings and plasma lipoprotein profile, ApoE-Sendai mice, not apoE KO mice, is a murine model for human LPG. This means that apoE variants are essential to LPG.