维格列汀对大鼠动脉内皮舒张功能的影响及其机制研究

Effect of vildagliptin on endothelium-dependent vasodilation in rat arteries and its mechanism

摘要:

目的：探讨维格列汀对大鼠血管舒张功能的影响及其可能的机制。方法：将雄性SD大鼠分为对照组和维格列汀组[6 mg/（kg·d）]，每组10只，连续干预6周。血管张力测定仪检测大鼠胸主动脉和肠系膜动脉的内皮依赖性舒张功能，酶标仪检测一氧化氮（nitric oxide，NO），Western blot和RT-PCR检测内皮型一氧化氮合酶（endothelial nitric oxide synthase，eNOS）蛋白水平和mRNA水平。结果：重复测量方差分析提示，胸主动脉和肠系膜动脉由乙酰胆碱（acetylcholine，ACh）诱导的内皮依赖性舒张在处理组间有统计学差异（F=25.388，P=0.001；F=15.713，P=0.005），在不同ACh浓度间有统计学差异（F=664.954，P=0.000；F=440.579，P=0.000），处理因素与浓度因素有交互作用（F=5.905，P=0.002；F=8.446，P=0.000），对照组和维格列汀组胸主动脉的最大舒张程度分别为（84.20±1.21）%和（92.18±1.02）%（t=5.167，P=0.000），肠系膜动脉的最大舒张程度分别为（86.57±2.21）%和（94.24±0.92）%（t=3.202，P=0.010）。动脉对ACh反应的敏感性增强（t=3.883，P=0.001；t=4.459，P=0.001）。与对照组相比，维格列汀组NO的含量升高（t=6.019，P=0.000；t=4.848，P=0.000）。维格列汀上调胸主动脉和肠系膜动脉eNOS蛋白水平（t=6.193，P=0.000；t=4.895，P=0.001）和mRNA水平（t=6.100，P=0.000；t=6.240，P=0.000）。结论：维格列汀可上调大鼠胸主动脉和肠系膜动脉eNOS转录及蛋白表达，增强动脉的舒张功能。

Abstract:

Objective：To investigate the effect of vildagliptin on vasodilation in rats and its mechanism. Methods：Male Sprague-Daw－ley rats were divided into control group（n=10） and vildagliptin group[6 mg/（kg·d），n=10]. These rats were treated for 6 months，and the thoracic aortas and mesenteric arteries were harvested at the end of the 6-month treatment for analysis. The endothelium-dependent vasodilation in the thoracic aorta and mesenteric artery was measured by wire myograph，the nitric oxide（NO） level was measured by colorimetry，and the protein and mRNA levels of endothelial nitric oxide synthase（eNOS） were determined by Western blot and RT-PCR，respectively. Results：The results showed that acetylcholine（ACh）-mediated endothelium-dependent vasodilation in the thoracic aorta and mesenteric artery was significantly different between groups（repeated measures ANOVA，F=25.388，P=0.001；F=15.713，P =0.005） and at different ACh concentrations（repeated measures ANOVA，F=664.954，P=0.000；F=440.579，P=0.000），with a significant interaction between treatment and concentration（F=5.905，P=0.002；F=8.446，P=0.000）. The maximum vasodilation of the thoracic aorta in the control group and the vildagliptin group was （84.20±1.21）% and （92.18±1.02）%，respectively（t=5.167，P=0.000）；the maxi－mum vasodilation of the mesenteric artery in the control group and the vildagliptin group was （86.57±2.21）% and （94.24±0.92）%，respectively（t=3.202，P=0.010）. The sensitivity to ACh of the arteries was improved（t=3.883，P=0.001；t= 4.459，P=0.001）. A signifi－cant increase in the NO level in the vildagliptin group was observed compared with that in the control group（t=6.019，P=0.000；t=4.848，P=0.000）. The protein level（t=6.193，P=0.000；t=4.895，P=0.001） and mRNA level（t=6.100，P=0.000；t=6.240，P=0.000） of eNOS in the thoracic aorta and mesenteric artery were up-regulated in the vildagliptin group. Conclusion：Vildagliptin can promote vasodilation in rat thoracic aorta and mesenteric artery by up-regulating eNOS transcription and expression.