高糖和胰岛素对内皮细胞产生一氧化氮的影响

Effects of High Glucose and High Insulin on Nitric Oxide Generation in Human Umbilical Vein Endothelial Cells

目的:探讨高胰岛素和(或)高糖对培养的人脐静脉内皮细胞(HUVEC)产生一氧化氮(NO)、血管紧张素Ⅱ(AngⅡ)和超氧阴离子(O2-)的影响。方法:不同浓度的葡萄糖和胰岛素加入体外培养的人脐静脉内皮细胞,24h后取细胞培养液分别测定NO、AngⅡ和O2-的浓度。结果:5.5mmol/L葡萄糖对内皮细胞NO、O2-产生无明显影响,25mmol/L葡萄糖使NO、O2-产生增加;10、100、1000mU/L的胰岛素使NO产生增加,但对O2-产生无影响。而在25mmol/L葡萄糖存在的情况下加入不同浓度(10、100、1000mU/L)的胰岛素,可使内皮细胞NO产生减少,使O2-产生明显增加。5.5、25mmol/L葡萄糖及各浓度的胰岛素均可使AngⅡ升高。25mmol/L葡萄糖与10、100、1000mU/L胰岛素合用组AngⅡ浓度升高。加入19.5mmol/L甘露醇对NO、AngⅡ和O2-无明显影响,除外高渗对结果的影响。结论:NO、AngⅡ和O2-平衡失调在胰岛素抵抗引起心血管疾病的发生、发展过程中具有重要的病理意义。

Objective： To investigate the effects of high glucose and high insulin on nitric oxide （NO）, angiotensin Ⅱ （Ang Ⅱ ） and superoside anion （O2-） generation in human umbilical vein endothelial cells （HUVECs）. Methods： HUVECs were incubated with different dosage glucose and insulin for 24 hours, and then NO, Ang Ⅱ and O2- in the supernatant were measured. Results： No effect was observed on NO and O2- generation in 5.5 mmol/L glucose. NO and O2- generation increased in 25 mmol/L glucose. NO generation increased in 10, 100, 1 000 mU/L insulin, and no effect was observed on O2- generation. NO generation decreased and O2- generation increased significantly in 25 mmol/L glucose and 10, 100, 1 000 mU/L insulin. Ang Ⅱ increased in 5.5 mmol/L or 25 mmol/L glucose and various dosage insulin. Ang Ⅱ increased in 25 mmol/L glucose and 10, 100, 1 000 mU/L insulin. There was no significant effect after adding 19.5 mmol/L manitol on NO, Ang Ⅱ and O2- generation, which excluded the effect of high osmosis. Conclusion： NO, Ang Ⅱ and O2- imbalance plays an important role in the development of cardiovascular disease caused by insulin resistance.