罗格列酮对糖尿病大鼠血管内皮损伤的保护作用与一氧化氮合酶抑制物的关系

Protective effect of rosiglitazone on endothelial cells and endogenous nitric oxide synthase inhibitor in diabetic rats

目的研究罗格列酮对链脲佐菌素(STZ)诱导的1型糖尿病大鼠血管内皮损伤的保护作用与内源性一氧化氮合酶(NOS)抑制物的关系。方法SD大鼠单次腹腔注射STZ(60mg·kg-1)诱发实验性1型糖尿病,检测血中血糖、血脂、非对称性二甲基精氨酸(ADMA)、肿瘤坏死因子-α(TNF-α)含量,并观察离体主动脉环的内皮依赖性舒张反应;ADMA孵育内皮细胞,检测细胞培养液中TNF-α。结果实验性1型糖尿病大鼠胸主动脉对乙酰胆碱(Ach)诱导的血管内皮依赖性舒张效应显著减弱,血中TNF-α与ADMA浓度显著升高,罗格列酮能显著改善糖尿病大鼠内皮依赖性舒张功能,降低血中TNF-α浓度,但不影响血脂、血糖与ADMA水平。在培养的人脐静脉内皮细胞,ADMA能显著升高培养液中TNF-α水平,罗格列酮(10,30μmol·L-1)能显著抑制TNF-α水平的升高。结论罗格列酮能改善链脲佐菌素诱导的1型糖尿病大鼠血管内皮依赖性舒张功能,其机制与抑制ADMA的致炎作用有关。

OBJECTIVE To determine the relationship between protective effect of rosiglitazone on the endothelium in streptozotocin-induced diabetic rats and endogenous nitric oxide synthase inhibitor. METHODS Diabetes was induced by a single intraperitoneal injection of streptozotocin(60 mg·kg~ -1) in Sprague-Dawley rats. Vasodilator responses to acetylcholine (Ach) in the isolated aortic rings were measured,and serum concentrations of glucose,lipid,nitric oxide(NO),asymmetric dimethylarginine (ADMA),and tumour necrosis factor-α (TNF-α) were determined. Human umbilical vein endothelial cell was cultured with ADMA and the concentration of TNF-α in the cultured medium was measured. RESULTS Vasodilator responses to Ach were decreased markedly and the serum concentrations of ADMA and TNF-α were increased significantly in streptozotocin-induced diabetic rats. Rosiglitazone (3,10 or 30 mg·kg~ -1) markedly reduced the inhibition of vasodilator responses to Ach and decreased the serum concentration of INF-α in diabetic rats,but had no effect on the serum concentrations of glucose,lipid and ADMA in diabetic rats. Incubation of HUECV with ADMA(30 μmol·L~ -1)significantly increased the concentration of TNF-α in the cultured medium,which was inhibited in the presence of rosiglitazone (10 or 30 μmol·L~ -1). CONCLUSIONS Rosiglitazone improves the endothelial function in streptozotocin-induced diabetic rats,and the protective effect of rosiglitazone on endothelium is related to the reduction of inflammatory reaction induced by ADMA.