Yang Zhi-Chun, Xia Ke, Wang Li, Jia Su-Jie, Li Dai, Zhang Zhe, Deng Shen, Zhang Xiao-Hong, Deng Han-Wu, Li Yuan-Jian
Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Xiang-Ya Road #110, Changsha 410078, China.
Microvasc Res. 2007 Mar;73(2):131-6. doi: 10.1016/j.mvr.2006.04.008. Epub 2006 Nov 13.
To investigate the effect of asymmetric dimethylarginine on erythrocyte deformability in streptozotocin-induced diabetic rats, a single intraperitoneal injection of streptozotocin (STZ, 65 mg/kg) in male Sprague-Dawley rats was carried out to induce diabetes and normal erythrocytes were incubated with asymmetric dimethylarginine or aortic rings from diabetic rats in the presence of L-arginine or vitamin E. We found that erythrocyte deformability was significantly decreased in diabetic rats. The levels of asymmetric dimethylarginine in plasma and erythrocytes of diabetic rats were elevated significantly from 2-week diabetic duration to 8-week diabetic duration. Nitric oxide in erythrocytes was decreased at 8-week diabetic duration while plasma nitric oxide remained unchanged all along. The content of malondialdehyde in erythrocytes of diabetic rats was increased. After incubation of erythrocytes with asymmetric dimethylarginine (10(-6) M) for 30 min, erythrocyte deformability and nitric oxide level in erythrocytes were decreased markedly. Reactive oxygen species and malondialdehyde production in erythrocytes were promoted by asymmetric dimethylarginine. Both L-arginine and vitamin E reversed the effects of asymmetric dimethylarginine. After incubation of erythrocytes with aortic rings from diabetic rats, erythrocyte deformability was decreased, which was attenuated by L-arginine. These results indicated that reduction of erythrocyte deformability in diabetic rats was associated with promoted oxidant stress as well as impaired nitric oxide synthesis by elevation of asymmetric dimethylarginine.
为研究不对称二甲基精氨酸对链脲佐菌素诱导的糖尿病大鼠红细胞变形性的影响,对雄性Sprague-Dawley大鼠单次腹腔注射链脲佐菌素(STZ,65mg/kg)以诱导糖尿病,并将正常红细胞与不对称二甲基精氨酸或糖尿病大鼠的主动脉环在L-精氨酸或维生素E存在的情况下进行孵育。我们发现糖尿病大鼠的红细胞变形性显著降低。糖尿病大鼠血浆和红细胞中不对称二甲基精氨酸的水平从糖尿病病程2周时到8周时显著升高。糖尿病病程8周时红细胞中的一氧化氮减少,而血浆一氧化氮一直保持不变。糖尿病大鼠红细胞中丙二醛的含量增加。用不对称二甲基精氨酸(10⁻⁶M)孵育红细胞30分钟后,红细胞变形性和红细胞中的一氧化氮水平显著降低。不对称二甲基精氨酸促进了红细胞中活性氧和丙二醛的产生。L-精氨酸和维生素E均逆转了不对称二甲基精氨酸的作用。用糖尿病大鼠的主动脉环孵育红细胞后,红细胞变形性降低,L-精氨酸可使其减弱。这些结果表明,糖尿病大鼠红细胞变形性降低与氧化应激增强以及不对称二甲基精氨酸升高导致的一氧化氮合成受损有关。