糖尿病小型猪三磷酸腺苷结合盒转运体A1表达的变化

Change of ATP Binding Cassette Transporter A1 Expression in Diabetic Minipigs

用贵州小香猪建立 2型糖尿病动物模型 ,探讨糖尿病小型猪三磷酸腺苷结合盒转运体A1(ABCA1)表达的变化 .采用高脂高蔗糖饲料喂养贵州小香猪 ,建立 2型糖尿病动物模型 .血浆总胆固醇、甘油三酯、高密度脂蛋白胆固醇和葡萄糖的浓度均用氧化酶法测定 ,血浆游离脂肪酸 (FFA)用比色法测定 ,采用逆转录 聚合酶链反应、蛋白质印迹和免疫组织化学分别检测ABCA1mRNA和蛋白质的表达 .喂养 6个月后 ,实验组与正常对照组比较 ,空腹血糖值明显升高 ;空腹胰岛素水平在头 3个月轻度升高 ,在第 6个月末其水平降低 ;血清总胆固醇、甘油三酯和游离脂肪酸水平升高 ;肝组织、冠状动脉、肾组织ABCA1表达上调 ,同时观测到糖尿病小型猪肝组织LXRα表达上调 .结果提示高脂高蔗糖饲料可引起小型猪脂质和糖代谢紊乱 ,并导致肝组织、冠状动脉和肾组织ABCA1表达上调以及肝组织LXRα表达上调 .

To establish a new animal model of the human type 2 diabetes mellitus and investigate the change of ATP binding cassette transporter A1 expression in diabetic minipigs, Chinese minipigs were fed a normal control diet ( CD) or a high fat/high sucrose diet (HFSD) for 6 months. Plasma total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C, triglycerides (TG) and glucose were determined by commercially enzymatic methods. Plasma free fatty acids (FFA) were measured by a colorimetric method. ABCA1 mRNA and protein level were determined by reverse trancriptase-polymerase chaim reaction (RT-PCR), Western blot and immunohistochemistry, respectively. After HFSD for 6 months, plasma serum total cholesterol, HDL cholesterol, FFA, triglyceride, and glucose in diabetic minipigs were increased compared with the control. Insulin level of diabetic minipigs was increased in the first 3 months and then decreased at the end of the 6th month. ATP binding cassette transporter A1 expression and liver X receptor alpha in diabetic minipigs was upregulated. HFSD may induce hyperglycemia, hypercholesterolemia, hypertriglyceridemia and upregulation of ATP binding cassette transporter A1 expression and liver X receptor alpha in diabetic minipigs.