肿瘤坏死因子α诱导的胰岛素抵抗对小鼠脂肪甘油三酯水解酶的影响  

Effects of tumor necrosis factor-α induced insulin resistance on adipose triglyceride lipase in mice

作　　者：程玉兰[1] 李伶[1] 杨刚毅[2] 石绍川[1] 陈渝[2] 朱伟[2] 孙逊[2] 

机构地区：[1]重庆医科大学检验系临床生化教研室教育部省部共建重点实验室,400016 [2]重庆医科大学附属第二医院内分泌科

出　　处：《中华医学杂志》2008年第34期2417-2421,共5页National Medical Journal of China

基　　金：国家自然科学基金资助项目（30771037）;重庆市教委科研基金资助项目（JK050304）

摘　　要：目的探讨肿瘤坏死因子α（TNF-α）诱导的胰岛素抵抗（IR）对糖脂代谢及脂肪甘油三酯水解酶（ATGL）的影响。方法健康雄性C57BL／6J小鼠随机分为2组，分别给予腹腔注射TNF-α6μg·kg^-1·d^-1（TNF组，20只）和等体积生理盐水（NC组，20只）共7d。采用2-脱氧-^3H葡萄糖（2-DOG）为示踪剂的扩展胰岛素钳夹技术评价小鼠胰岛素敏感性和糖代谢变化，用逆转录聚合酶链反应（RT—PCR）和蛋白质印迹法分别测定代谢相关基因ATGL、激素敏感性脂酶（HSL）、过氧化物酶体增殖物激活受体γ（PPARγ）等组织mRNA或血浆蛋白表达水平的变化。结果TNF-α处理后，小鼠空腹血糖（FBG）、血浆胰岛素和游离脂肪酸（FFA）水平均增高。在胰岛素钳夹术中，TNF组血浆胰岛素水平明显高于NC组[（341．7±17．7）vs（84．7±5．5）mU／L，P〈0．01]，胰岛素对FFA的抑制作用明显障碍[FFA，TNF组：（0．82±0．03）mmol／L，NC组：（0．43±0．07）mmol／L，P〈0．01]。TNF组葡萄糖输注率（GIR）明显低于NC组[（39．1±2．3）vs（54．2±2．2）mg·kg^-1·min^-1，P〈0．01]，骨骼肌葡萄糖摄取率（MGU）也明显低于NC组[（15．8±1．7）vs（20．9±2．5）μmol·100g^-1·min^-1，P〈0．01]。TNF组脂肪组织ATGL mRNA表达明显低于对照组（0．85±0．09vs1．37±0．12，P〈0．01），ATGL蛋白水平也明显低于对照组（0．53±0．03vs0．65±0．05，P〈0．05）。TNF组小鼠脂肪组织PPARγ mRNA表达明显低于对照组（0．83±0．07VS1．07±0．07，P〈0．05）。结论在TNF-α诱导的IR中，ATGL在脂代谢相关通路中起着调控作用。Objective To investigate the effects of tumor necrosis factor （TNF）-α induced insulin resistance （IR） on glucose and lipid metabolism and adipose triglyceride lipase （ATGL）. Methods Forty male C57BL/6J mice were randomly divided into 2 equal groups： TNF-α group with undergoing intraperitoneal injection of TNF-α 6 μg · kg^-1 · d^-1 for 7 days and normal control （NC） group with saline injection. Hyperinsulinemic-euglycemic clamp technique combined with 2-deoxy-[ ^3H] glucose as a tracer was used on 20 mice, 10 from each group, to examine the fasting blood glucose （ FBG）, plasma insulin （INS）, total cholesterol （TC）, triglyceride （TG）, and free fatty acid （FFA）. The glucose infusion rate （GIR） was recorded. Other 20 mice, 10 in each group, were killed with their adipose and/or muscle tissues taken out. RT-PCR was used to detect the mRNA expression of ATGL, hormone-sensitive lipase （HSL）, carnitine palmitoyl transferase-1 （CPT-1）, and peroxisome proliferator activated receptor-α （PPAR-γ）. Western blotting was used to measure the protein expression of ATGL. Muscle glucose uptake （MGU） was measured. Results After TNF-α treatment, the FBG, plasma INS, and FFA were significantly elevated in the TNF group compared with the NC group （ all P 〈 0.05 ）. During the steady-state of clamp test, the plasma INS level of the TNF group was （ 341.7 ± 17.7 ） mU/L, significantly higher than that of the NC group [（84.7 ±5.5） mU/L,P〈0.01]. The FFA level of the TNF group was （0.82±0.03） mmol/L, significantly higher than that of the NC group [ （0.43 ± 0.07） mmol/L,P 〈0.01 ] . The GIR of the TNFgroup was （ 39.1 ± 2.3 ） mg· kg ^- 1 · min^-1 , sigmficantly lower than that of the NC group [ （ 54.2 ± 2.2 ） mg·kg^-1 ·min^-1,P〈0.01]. The MGU level of the TNF group was （15.8 ±1.7）μmol · 100 g^-1 min^ - 1, significantly lower than that of the NC group [ （ 20.9 ± 2.5 ） μmol · 100 g^ - 1 · min^ -1, p 〈 0.01 ]. The ATGL mR

关 键 词：肿瘤坏死因子 胰岛素抗药性 脂代谢 脂肪甘油三酯水解酶 

分 类 号：R686[医药卫生—骨科学]