2型糖尿病大鼠主动脉内皮细胞氧化损伤及缬沙坦的保护作用

目的探讨2型糖尿病大鼠氧化应激与主动脉内皮细胞损伤的关系,观察缬沙坦对两者的影响。方法SD大鼠,用长期高能量饮食加小剂量注射链脲佐菌素(STZ)的方法复制模型。注射STZ12wk末,将大鼠分为3组:正常组、糖尿病组、缬沙坦治疗组(24mg·kg-1·d-1,灌胃给药8wk)。在注射STZ12和20wk末,检测大鼠的内皮依赖性血管舒张反应及主动脉内皮形态,血清超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)活性,丙二醛(MDA)和一氧化氮(NO)含量,以及主动脉一氧化氮合酶(NOS)基因表达情况。结果①12wk末,糖尿病大鼠主动脉对低浓度乙酰胆碱(ACh)舒张反应减弱,局部内皮隆起,血清SOD、GSH-Px活性增强,MDA和NO含量增加,主动脉iNOS mRNA表达明显上调,eNOS mRNA表达无明显改变。②20wk末,糖尿病大鼠主动脉对各浓度ACh的反应性均减弱,主动脉内皮变性、坏死,血清SOD、GSH-Px活性减弱,MDA含量进一步增加,NO含量下降,主动脉iNOS mRNA表达仍升高,eNOS mRNA表达降低,缬沙坦治疗后能减轻主动脉病变,改善血清SOD、GSH-Px、MDA、NO及主动脉NOS mRNA表达的异常。结论糖尿病大鼠的氧化应激和NO系统的紊乱参与了主动脉病变过程,增强机体抗氧化能力及调节NO生成可能是缬沙坦发挥主动脉保护作用的机制之一。

Aortic endothelial cells injury induced by oxidative stress in type 2 diabetes rats and the protective effect of valsartan

Aim To investigate the relationship between oxidative stress and the aortic endothelial cells injury in type 2 diabetes rats,as well as the effect of valsartan. Methods The type 2 diabetic models were induced by low dose of streptozotocin (STZ) with high-energy diet.12 weeks after injecting STZ, rats were randomly divided into three groups: normal control, diabetes control and valsartan (24 mg·kg-1·d-1, 8 weeks, ig.) treated diabetes. At the 12th and 20thweek end, such indices as the endothelium-dependent vasodilation and the shape of aorta endothelium, the serum contents of SOD, GSH-Px , MDA and NO, and the level of NOS gene expression in aorta were measured. Results ① At the 12th weekend,in the diabetes group, the relaxation of aortic rings to low concentration of Ach declined, the aortic endothelial cells intumesced, contents of serum SOD, GSH-Px, MDA and NO significantly increased, the expression of iNOS mRNA in aorta obviously up-regulated while the expression of eNOS mRNA showed no change. ② At the 20th weekend,in the diabetes control group, the dilatory reactivity of aortic rings decreased to each concentration of Ach, the aortic endothelium appeared degenerative and necrotic, activities of SOD and GSH-Px decreased as well as the content of NO, the content of MDA increased continuously, and the iNOS mRNA expression up-regulated while eNOSmRNA expression down-regulated. Valsartan could regress the aggravation and improve contents of serum SOD, GSH-Px, MDA, NO and NOS mRNA of the aorta. Conclusion The oxidative stress and abnormality of NO participate the process of aortic endothelial cell injury. Valsartan plays a protective role partially through enhancing antioxidation effect and adjusting NO production.