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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 compare the blood glucose and vasoconstriction and diastolic function of Goto-Kakizaki (GK) rats with non-obese type 2 diabetes mellitus (DM) at different ages and to explore the possible mechanism of their functional changes. Methods Six male GK rats (40 weeks old) were used in this experiment. Six rats in each group were used as controls. The body weight, blood glucose and awake caudal arterial pressure and heart rate were recorded. The thoracic aorta was excised from anesthetized thoracotomy, the contractile function and endothelium-dependent and non-endothelium-dependent diastolic function of isolated vascular rings were measured, Insulin levels were measured. Results ① Compared with Wistar rats, blood glucose in GK rats was significantly higher at 6 weeks ([8.1 ± 0.4] vs (5.8 ± 0.3) mmol / L, P <0.01] ± 0.4) mmol / L, P <0.01], and there was no significant change in blood pressure and insulin levels. The heart rate of 40-week-old GK rats was significantly higher than that of Wistar rats. ② The maximal contractile responses of GK rats with different ages to 60mmol / L potassium chloride and 1 × 10-6 ~ 1 × 10-5mol / L phenylephrine decreased. However, the GK vessels Contractile responses to low doses of 1 × 10-8 mol / L phenylephrine increased. ③ The vasodilatation of acetylcholine and sodium nitroprusside in two groups of GK rats at different ages was significantly higher than that of Wistar rats. The vasodilatory responses to acetylcholine in 6-week-old GK rats were completely blocked by nitric oxide synthase (NOS) blockers. The vasodilatory response to acetylcholine in the 40-week-old GK rats was not completely blocked by NOS blocker. The rest of the relaxation was blocked by heme oxygenase (HO) blockers (P <0.01). Conclusions The up-regulation of NOS activity may be the main mechanism of endothelium-dependent vasodilation in the thoracic aorta of GK rats. The enhancement of vasodilatation in aged GK rats may be due to the involvement of NOS and HO systems.