中文摘要：

目的：研究不同周龄脂蛋白脂酶（LPL）基因敲除小鼠糖脂代谢情况,并探究其胰岛素抵抗的可能机制。方法分别选取16周和40周 LPL 基因敲除杂合子小鼠（LPL＋/-）和野生型（WT）C57小鼠作为实验对象,将其分为4组：16周 LPL＋/-组（n=6）、16周 WT 组（n=6）、40周 LPL＋/-组（n =6）和40周WT 组（n=6）。注射肝素后,分别测定 LPL＋/-小鼠及 WT 小鼠血清 LPL 活性；检测4组小鼠血清甘油三酯和游离脂肪酸水平；行腹腔葡萄糖耐量试验（IPGTT）监测血糖变化,计算葡萄糖曲线下面积（AUCG）和稳态模型评估的胰岛素抵抗指数（HOMA-IR）、稳态模型评估的β细胞功能指数（HOMA-β）,评价胰岛素敏感性及胰岛β细胞功能；采用比色法测定血清丙二醛和总抗氧化力水平；用二氢乙啶（DHE）荧光染色法检测肝脏和骨骼肌中活性氧簇（ROS）水平。结果16 和40周龄 LPL＋/-组小鼠 LPL 活性均明显低于同周龄WT 组小鼠（P＜0.05）。40周龄 LPL＋/-组小鼠血清甘油三酯和游离脂肪酸水平显著高于同周龄 WT 组小鼠（P＜0.05）,也明显高于16周龄 LPL＋/-组小鼠甘油三酯、游离脂肪酸水平（P＜0.05）。与同周龄 WT 组比较,40周龄 LPL＋/-组小鼠 IPGTT 30、120 min 血糖明显上升（P＜0.05）,空腹胰岛素、HOMA-IR 显著升高（P＜0.05）。40周龄 LPL＋/-组小鼠血清丙二醛明显升高（P＜0.05）,总抗氧化力显著降低（P＜0.05）。16周龄 LPL＋/-组小鼠骨骼肌中 ROS 表达水平显著增加,而40周龄 LPL＋/-小鼠中肝脏、骨骼肌 ROS 水平均明显高于同周龄 WT 组小鼠。结论 LPL＋/-小鼠随着年龄增长,脂代谢紊乱加重,血糖升高且出现明显胰岛素抵抗。血脂异常的 LPL＋/-小鼠产生的胰岛素抵抗可能与氧化应激有关。

英文摘要：

Objective To investigate the glucolipid metabolism in lipoprotein lipase （LPL） gene knockout mice, and to explore the possible mechanisms of insulin resistance. Methods 16- and 40-week old LPL gene knockout heterozygous mice（ LPL ＋ / -） and wild type （ WT） C57 mice were selected and divided into 4 groups：16-week LPL＋ / -（n=6）, 16-week WT（n = 6）, 40-week LPL＋ / -（n = 6）, and 40-week WT（n = 6） group. LPL activity of post-heparin serum was examined. Serum triglyceride（ TG） and free fatty acid（ FFA） were measuzed. Intraperitoneal glucose tolerance test（IPGTT） in 4 groups of mice were performed. The glucose area under the curve （AUCG） and homeostasis model assessment for insulin resistance index and β-cell function index （ HOMA-IR, HOMA-β） were calculated to evaluate insulin sensitivity and the function of islet β-cells. Serum malondialdehyde （MDA） and total antioxidant capacity （ TAOC） levels were determined by means of colorimetric method. Using dihydroethidium（ DHE） fluorescent staining method, reactive oxygen species （ ROS） levels in liver and skeletal muscle were determined. Results LPL activity levels of both 16- and 40-week LPL＋ / - mice were significantly lower than that in WT mice of the same age. Serum TG and FFA of 40-week old LPL＋ / - mice were significantly higher than those in WT mice of the same age（P〈0. 05）, and they were also higher than those of 16-week old LPL＋ / - mice（P〈0. 05）. IPGTT showed that compared with WT mice, blood glucose level in LPL＋ / - mice was significantly higher than that in WT group at 30 and 120 minute（P〈0. 05）, and fasting insulin and HOMA-IR were increased significantly（P〈0. 05）. Serum MDA of 40-week old LPL＋ / - mice was evidently higher than that in WT mice by the same week（P〈0. 05）, while TAOC level was lower than that of WT mice （P〈0. 05）. ROS in skeletal muscle of 16-week old LPL＋ /- mice was significantly increased. Meanwhile, ROS in both liver and s