不同年龄非肥胖2型糖尿病Goto-Kakizaki大鼠离体主动脉血管收缩与舒张功能  

Isolated Aortic Vessel Function in Non-obese Type 2 Diabetic Goto-Kakizaki Rats at Different Ages

作　　者：乔丛蓁[1] 张宁[2] 钟梅芳 包阳扬[1] 吴国忠 张川 陈红[1] 

机构地区：[1]上海交通大学医学院药理学教研室 [2]第二军医大学药学院 [3]上海医药高等专科学校,上海20002

出　　处：《中华高血压杂志》2010年第5期474-480,共7页Chinese Journal of Hypertension

基　　金：国家自然基金项目(30770848及30971154)

摘　　要：目的观察比较非肥胖2型糖尿病Goto-Kakizaki(GK)大鼠不同年龄时的血糖及血管收缩与舒张功能,探讨其功能变化的可能机制。方法实验采用6与40周龄雄性GK大鼠,每组6只,同龄Wistar大鼠作对照。记录体质量、血糖以及清醒状态下的尾动脉血压及心率后,麻醉开胸剪取胸主动脉,检测离体血管环的收缩功能及内皮依赖性与非内皮依赖性舒张功能,并留取血清测定胰岛素水平。结果①与Wistar大鼠比较,GK大鼠的血糖在6周龄[(8.1±0.4)比(5.8±0.3)mmol/L,P<0.01]、40周龄[(17.3±0.8)比(5.6±0.4)mmol/L,P<0.01]均明显升高,血压及胰岛素水平未见明显变化,40周龄GK大鼠心率较Wistar大鼠明显升高。②两组不同年龄GK大鼠血管对60mmol/L氯化钾及1×10-6～1×10-5mol/L苯肾上腺素的最大收缩反应均减弱,但去内皮后40周龄组GK血管对低剂量1×10-8mol/L苯肾上腺素的收缩反应增强。③两组不同年龄GK大鼠血管对乙酰胆碱及硝普钠的舒张反应均较Wistar大鼠显著增强。④6周龄GK大鼠血管对乙酰胆碱的舒张反应可被一氧化氮合酶(NOS)阻断剂完全阻断。而40周龄GK大鼠血管对乙酰胆碱的舒张反应不能完全被NOS阻断剂阻断,剩余的舒张部分可进一步被血红素加氧酶(HO)阻断剂阻断(P<0.01)。结论 NOS系统活性的上调可能是GK大鼠胸主动脉内皮依赖性血管舒张功能增强的主要机制,高龄GK大鼠的血管舒张功能增强可能由于NOS系统与HO系统共同参与调控所致。Objective To observe isolated aortic vessel function in the non-obese type 2 diabetic Goto-Kakizaki（GK）rats at different ages.Methods GK rats at ages of 6 and 40 weeks and Wistar control rats at the same ages were used.Blood glucose,serum insulin,systolic blood pressure and heart rate of both control Wistar rats and diabetic GK rats were recorded.The thoracic aortic rings from both control and diabetic GK rats were isolated and vessel function was assessed in vitro.Results ① Compared with non-diabetes controls,blood glucose levels of GK rats at both ages were higher [（8.1±0.4）vs（5.8±0.3）mmol/L in 6 week and（17.3±0.8）vs（5.6±0.4）mmol/L in 40 week old GK rats,all P0.01] with no significant changes in insulin levels.There was no significant difference in blood pressure between GK and control rats.However,the heart rate of GK rats was higher than control rats.② Thoracic aorta rings from GK rats at 6 and 40-week of ages showed decreased maximal contraction responses to 60 mmol/L potassium chloride and to 1×10-6-1×10-5 mol/L phenylephrine（PE）.However a higher contraction response to lower concentration of PE（1×10-8 mol/L）was observed in 40 week old GK aortic rings without endothelium.③ The relaxation responses of the vessel to acetylcholine（ACh）and sodium nitroprusside were enhanced in both ages of GK rats.④ In 6-week-old GK rats,the enhanced vasodilatation to ACh was completely inhibited by nitric oxide synthase（NOS）blocker.While in 40 week old GK,ACh-induced vasodilatation was not completely blocked and the remaining（5.2±0.8）% relaxation was inhibited by incubation with heme oxygenase（HO）blocker.Conclusion These results reveal that up-regulation of NOS may be responsible for the enhanced endothelium-dependent vasorelaxation in GK rats.Besides NOS systems,HO systems possibly act concomitantly as the compensatory mechanisms to maintain normal vascular reactivity in the aged GK rats.

关 键 词：非肥胖2型糖尿病 血管收缩与舒张功能 一氧化氮合酶 血红素加氧酶 Goto-Kakizaki大鼠 

分 类 号：R587.1[医药卫生—内分泌]