胰岛素抵抗大鼠内皮依赖性血管舒张功能研究

目的　探讨高脂饲料诱导胰岛素抵抗 (IR )动物模型的内皮功能变化及其机制。方法　高脂饲料喂养大鼠 4周 ,建立IR动物模型 ,并用正葡萄糖高胰岛素钳夹技术的葡萄糖输注率 (GIR)评价IR。观察大鼠离体主动脉对乙酰胆碱 (Ach)依赖性血管舒张功能反应和一氧化氮合酶 (NOS) 一氧化氮 (NO) cGMP功能状态。结果　 ( 1)高脂饲料组大鼠的GIR显著低于正常饲料组大鼠 (P <0 .0 1) ,且GIR水平与大鼠体重呈显著负相关 (r =-0 .75 ,P <0 .0 1)。 ( 2 )高脂饲料组大鼠离体主动脉条对Ach依赖性血管舒张功能反应显著降低 ,最大舒张反应降低 13 .8% (P <0 .0 1) ,高脂饲料组大鼠主动脉NO及cGMP浓度明显低于普通饲料组大鼠 (均P <0 .0 5 ) ,两组大鼠主动脉NOS浓度无明显差别。 ( 3 )大鼠主动脉条对Ach依赖性血管舒张功能反应与NO水平呈显著负相关 (r =-0 .65 ,P <0 .0 5 )。结论　 ( 1)应用正葡萄糖高胰岛素钳夹技术显示 ,在高脂饲料饲养 4周的大鼠建立了IR大鼠模型。 ( 2 )高脂饲料饲养大鼠的内皮细胞功能减弱 ,其机制与NO水平降低密切相关。

On the endothelium-dependent vasodilation function in insulin-resistant rats

Objective To observe the change of endothelium-dependent vasodilatation function and to explore its mechanism in insulin-resistant (IR) rats induced by high fat feed. Methods (1) IR rat model was established by high fat feed for 4 weeks and IR was evaluated by glucose infusion rate (GIR) of euglycemic hyperinsulinemic clamp technique. (2) Acetylcholine (Ach)-dependent vasodilation response and nitric oxide synthase (NOS)-nitric oxide (NO)-cGMP function status were observed in isolated aorta of rats. Results (1) GIR was obviously lower in high fat feed group than that in routine feed group (P<0.01), and there was a significantly negative correlation between GIR and the weight of rats (r=-0.75, P<0.01). (2) In high fat feed group Ach-dependent vasodilation response of isolated aorta was markedly decreased and the maximum dilating response was decreased by 13.8% (P<0.01). The concentrations of NO and cGMP in the aorta of high fat feed group were lower than those in routine feed group (both P<0.05), but it was not significantly different between activities of NOS in aorta of 2 groups of rats. (3) There was a significantly negative correlation between the Ach-dependent vasodilation response and NO level (r=-0.65, P<0.05). Conclusion (1) IR rat model is established by high fat feed for 4 weeks and verified by euglycemic hyperinsulinemic clamp technique. (2) Endothelial function is decreased in rats by feeding high fat food and the change of endothelial function is related to the decreased NO level.