高游离脂肪酸血症通过氧化应激导致胰岛β细胞功能受损  

Elevated circulating free fatty acids level causes pancreatic islet β-cell dysfunction via oxidative stress

作　　者：张玄娥[1] 余叶蓉[1] 柯柳[1] 张祥迅[1] 

机构地区：[1]四川大学华西医院内分泌科,成都610041

出　　处：《中华内分泌代谢杂志》2009年第1期13-16,共4页Chinese Journal of Endocrinology and Metabolism

基　　金：国家自然科学基金资助项目（30570874）

摘　　要：目的研究高游离脂肪酸（FFA）血症对胰岛β细胞功能的影响。方法正常雄性SD大鼠随机分为3组：对照组输注生理盐水，FFA组输注脂肪乳，氮乙酰半胱氨酸（NAC）干预组在输注脂肪乳的同时加用NAC。持续输液2～4天，行静脉葡萄糖耐量试验（IVGTT）和胰腺组织表面灌注试验评价在体及离体情况下胰岛β细胞胰岛素分泌功能。结果胰腺组织表面灌注结果显示，FFA组脂肪乳输注2天，基础状态下的胰岛素分泌较对照组增加[（55．5±19．4US27．4±6．7）mlU／L，P〈0．01]，而葡萄糖刺激的胰岛素分泌（GSIS）与对照组并无差别；延长脂肪乳输注到4天，高FFA刺激基础胰岛素分泌的作用消失，且GSIS明显抑制[（46．8±33．0vs214．7±27．4）mlU／L，P〈0．05]。IVGTT结果亦显示脂肪乳输注4天后胰岛素分泌功能受到抑制。但在脂肪乳输注的同时加用抗氧化剂NAC可使β细胞GSIS峰值部分恢复[（165．4±14．8）mIU／L，P〈0．01]。结论循环中FFA水平增高可能通过激活氧化应激导致胰岛β细胞功能受损。Objective To evaluate the effeets of elevated circulating free fatty acids （FFA） level on basal and glucose stimulated insulin secretion （GSIS） of islet β-cell and to explore the pathophysiologieal link between FFA and impaired β-cell dysfunction. Methods Male SD rats underwent infusions with normal saline （ C group） , intralipid＋heparin （FFA group） and N-acetylcysteine ＋ FFA （NAC group） for 2-4 days. Insulin secretion from pancreatic tissues was evaluated during intravenous glucose tolerance test and isolated pancreas perfusion test at the end of 2 and 4 days infusion. Results After 2 days infusion, the basal insulin secretion from isolated perfused pancreas was increased in FFA group [ （55.5 ± 19.4 vs 27.4±6.7 ） mU/L, P〈0.01 ], but the response to 16.7 mmol/L glucose in isolated perfused pancreas was similar in FFA and C groups. The peak value during GSIS was inhibited by 4 days FFA infusion [ （46.8±33.0 vs 214.7 ±27.4）mIU/L,P〈0.05 ]. GSIS was also decreased in FFA group compared with C group in IVGTF. After interfered with NAC, GSIS was partly recovered [ （165.4± 14.8 ）mIU/L, P〈0.01 ]. Conclusion Elevated circulating FFA levels may contribute to the abnormality of pancreatic islet β-cell through oxidative stress.

关 键 词：脂肪酸类 非酯化 胰岛Β细胞功能 氧化应激 

分 类 号：R686[医药卫生—骨科学]