Department of Basic Nursing Science, School of Nursing, Korea University, Seoul, Republic of Korea.
J Appl Physiol (1985). 2018 May 1;124(5):1274-1283. doi: 10.1152/japplphysiol.01018.2017. Epub 2018 Feb 22.
Although stress is one of the risk factors of diabetes, few studies have assessed the effects of stress on diabetic rats. This study, therefore, analyzed differences in cardiovascular-related factors among control, nonstressed diabetic, and stressed diabetic rats as well as assessed the effects of linalyl acetate (LA) on stressed diabetic rats. Male Sprague-Dawley rats were subjected to immobilization stress throughout the experimental period, and diabetes was induced on day 15 by a single injection of streptozotocin. After confirming the induction of diabetes, stressed diabetic rats were administered LA (10 or 100 mg/kg) or metformin (500 mg/kg) for the last 7 days. Compared with nonstressed diabetic rats, stressed diabetic rats had significantly lower body weight, body fat percentage, ACh-induced vasorelaxation, systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and NF-κB expression as well as increased serum nitrite concentration. Although metformin increased serum insulin concentration significantly, 100 mg/kg LA showed only an increasing tendency. However, treatment with 100 mg/kg LA not only reduced serum glucose and NF-κB expression, but also restored ACh-induced vasorelaxation, SBP, DBP, HR, AMP-activated protein kinase expression, and serum nitrite almost to control levels. Importantly, 100 mg/kg LA was more effective than metformin in ameliorating serum glucose, endothelial nitric oxide synthase expression, HR, and serum nitrite. These findings suggest that chronic stress can aggravate endothelial dysfunction and hemodynamic alterations in diabetes and that LA may have potent therapeutic efficacy in diabetic patients with cardiovascular disease complications or chronic stress. NEW & NOTEWORTHY To our knowledge, this is the first study to assess the effects of linalyl acetate (LA) on cardiovascular-related factors in diabetic rats exposed to chronic stress. Treatment with LA restored acetylcholine-induced vasorelaxation, blood pressure, heart rate, and AMP-activated protein kinase and serum nitrite levels. The present results suggest that LA may have potent therapeutic efficacy in diabetic patients with complications of cardiovascular disease or chronic stress.
虽然压力是糖尿病的风险因素之一，但很少有研究评估压力对糖尿病大鼠的影响。因此，本研究分析了对照组、非应激糖尿病组和应激糖尿病组大鼠心血管相关因素的差异，并评估了乙酸芳樟酯（LA）对应激糖尿病大鼠的影响。雄性 Sprague-Dawley 大鼠在整个实验期间接受束缚应激，第 15 天通过单次注射链脲佐菌素诱导糖尿病。在确认糖尿病诱导后，应激糖尿病大鼠最后 7 天给予 LA（10 或 100mg/kg）或二甲双胍（500mg/kg）。与非应激糖尿病大鼠相比，应激糖尿病大鼠的体重、体脂百分比、ACh 诱导的血管舒张、收缩压（SBP）、舒张压（DBP）、心率（HR）和 NF-κB 表达明显降低，血清硝酸盐浓度增加。虽然二甲双胍显著增加血清胰岛素浓度，但 100mg/kg LA 仅显示出增加的趋势。然而，用 100mg/kg LA 治疗不仅降低了血清葡萄糖和 NF-κB 表达，而且还恢复了 ACh 诱导的血管舒张、SBP、DBP、HR、AMP 激活蛋白激酶表达和血清硝酸盐几乎达到对照水平。重要的是，100mg/kg LA 在改善血清葡萄糖、内皮型一氧化氮合酶表达、HR 和血清硝酸盐方面比二甲双胍更有效。这些发现表明，慢性应激会加重糖尿病患者的内皮功能障碍和血流动力学改变，而 LA 可能对患有心血管疾病并发症或慢性应激的糖尿病患者具有潜在的治疗效果。
