Yamanouchi J, Takatori A, Itagaki S, Kawamura S, Yoshikawa Y
Department of Biomedical Science, Graduate School of Agricultural and Life Sciences, University of Tokyo, Japan.
Exp Anim. 2000 Oct;49(4):267-74. doi: 10.1538/expanim.49.267.
Syrian hamsters of the APA strain (APA hamsters) have recently been shown to have atheromatous lesions in the aortic arches under diabetic condition induced by a single injection of streptozotocin (SZ). In that model, fatty streaks, which are the initial lesions of atherogenesis, develop by 6 weeks after the injection (WAI). In this study, we evaluated plasma lipid concentrations and lipoprotein profiles in diabetic APA hamsters at 6 WAI to reveal the early stage of atherogenesis clinicopathologically. As a result, by biochemical analysis, hyperglycemic APA hamsters showed signs of hypercholesterolemia and hypertriglyceridemia. Low-density lipoprotein (LDL) cholesterol significantly increased, but high-density lipoprotein (HDL) cholesterol significantly decreased. Agarose gel electrophoresis showed an obvious increase in the fractions of chylomicron, LDL and abnormal lipoprotein. Plasma LDL in diabetic animals was in a state more susceptible to oxidization. In addition, a significant increase in glycated LDL was also found in the diabetic animals by enzyme linked immunosorbent assay (ELISA). Moreover, lipid peroxidation product (4-hydroxynonenal (4 HNE))-adducted proteins and advanced glycation end-products (AGE) were immunohistochemically detected in the foam cells of the fatty streaks. These results revealed that diabetic APA hamsters had hyperlipidemia characterized by increases in chylomicron, LDL and abnormal lipoprotein, and suggested that oxidized LDL and/or glycated LDL might be actively uptaken by macrophages and play an important role in the initial stage of atherogenesis.
最近研究表明，单次注射链脲佐菌素（SZ）诱导糖尿病状态下的APA品系叙利亚仓鼠（APA仓鼠）主动脉弓出现动脉粥样硬化病变。在该模型中，动脉粥样硬化起始病变——脂肪条纹在注射后6周（WAI）出现。在本研究中，我们评估了糖尿病APA仓鼠在6 WAI时的血浆脂质浓度和脂蛋白谱，以从临床病理学角度揭示动脉粥样硬化的早期阶段。结果显示，通过生化分析，高血糖的APA仓鼠出现高胆固醇血症和高甘油三酯血症迹象。低密度脂蛋白（LDL）胆固醇显著升高，而高密度脂蛋白（HDL）胆固醇显著降低。琼脂糖凝胶电泳显示乳糜微粒、LDL和异常脂蛋白组分明显增加。糖尿病动物的血浆LDL更易处于氧化状态。此外，通过酶联免疫吸附测定（ELISA）发现糖尿病动物的糖化LDL也显著增加。而且，在脂肪条纹的泡沫细胞中通过免疫组织化学检测到脂质过氧化产物（4-羟基壬烯醛（4-HNE））加合物蛋白和晚期糖基化终产物（AGE）。这些结果表明，糖尿病APA仓鼠存在以乳糜微粒、LDL和异常脂蛋白增加为特征的高脂血症，并提示氧化LDL和/或糖化LDL可能被巨噬细胞主动摄取，并在动脉粥样硬化的初始阶段发挥重要作用。
