糖尿病大鼠病程的不同时期血中一氧化氮合酶抑制物含量变化  

The Changes in Serum Concentration of Endogenous Inhibitor of Nitric Oxide Synthase at Different Stages of Diabetic Duration in Streptozotocin Induced Diabetic Rats

作　　者：熊燕[1] 苑利伟[1] 付云峰[1] 付四海[1] 周宏灏[2] 

机构地区：[1]中南大学药学院药理学教研室,湖南省长沙市410078 [2]中南大学临床药物研究所,湖南省长沙市410078

出　　处：《中国动脉硬化杂志》2003年第1期22-26,共5页Chinese Journal of Arteriosclerosis

基　　金：国家自然科学基金 ( 39970 848)资助

摘　　要：为了探讨糖尿病病程长短和代谢控制对血中内源性一氧化氮合酶抑制物非对称性二甲基精氨酸浓度的影响 ,本实验采用链脲佐菌素诱导 2、4和 8周的糖尿病大鼠 ,用高效液相色谱测定血中非对称性二甲基精氨酸和L 精氨酸浓度 ;用离体胸主动脉环检测乙酰胆碱诱导的内皮依赖性舒张 ;并检测血糖、糖基化血清蛋白和血清脂过氧化产物丙二醛浓度以反映代谢控制。结果发现 ,2周的糖尿病大鼠血中非对称性二甲基精氨酸浓度明显高于正常组 ( 3 .71± 0 .44 μmol L比 1.0 4± 0 .46μmol L ,P <0 .0 1) ,并持续到 4～ 8周 (第 4周 3 .5 4± 1.70 μmol L比 0 .95± 0 .13 μmol L ,第 8周 3 .2 1± 1.13 μmol L比 1.0 3± 0 .2 0 μmol L ,所有P <0 .0 1) ;而血中一氧化氮合酶底物L 精氨酸浓度在三个时程的糖尿病组和正常组之间并无明显区别 (P >0 .0 5 ) ;因此 ,2～ 8周糖尿病大鼠血中L 精氨酸与非对称性二甲基精氨酸的比值明显低于正常对照组 (P <0 .0 0 1)。此外 ,糖尿病大鼠血中内源性非对称性二甲基精氨酸升高伴随着代谢控制和血管环内皮依赖性舒张反应的降低。此结果提示 ,2～ 8周的糖尿病大鼠血中内源性非对称性二甲基精氨酸升高程度与糖尿病持续时间长短无明显关系 。Aim To investigate the time-dependent changes in serum concentrations of endogenous inhibitor of nitric oxide synthase (NOS) asymmetric dimethylarginine (ADMA) in streptozotocin-induced diabetic rats and age-matched control rats, and to determine whether elevated endogenous ADMA is related to metabolic control and is implicated in the endothelium-dependent vasodilation dysfunction of diabetic rats at different stage of diabetic duration. Methods Serum levels of ADMA and L-arginine were measured by high-performance liquid chromatography at stages of 2-, 4- and 8-week diabetic duration. Thoracic aortic rings from diabetic rats with different diabetic duration and their age-matched control rats were studied for endothelium-dependent relaxation response to acetylcholine in vitro. Serum concentrations of glucose, glycosylated serum protein, and malondialdehyde, derived from lipid peroxidation were also examined to estimate metabolic control. Results Serum levels of ADMA significantly elevated in diabetic rats with 2-, 4-, and 8-week diabetic duration compared with their age-matched control rats(3.71±0.44 μmol/L vs 1.04±0.46 μmol/L for 2-week,3.54±1.70 μmol/L vs 0.95 ±0.13 μmol/L for 4-week,3.21±1.13 μmol/L vs 1.03±0.20 μmol/L for 8-week,n=5～6,all P<0.01), whereas serum levels of L-arginine were not different between control and diabetic rats at stages of 2-, 4-, and 8-week diabetic duration. Accordingly, the ratio of L-arginine and ADMA in diabetic rats was lower than that in their age-matched control rats. This elevation of ADMA was accompanied by impairment of relaxation response to acetylcholine of aortic rings in diabetic rats. Serum levels of glucose, glycosylated serum protein, and malondialdehyde were significantly increased in parallel with the elevation of ADMA in diabetic rats with 2-, 4-, and 8-week diabetic duration compared with their age-matched control rats. Conclusion These results reveal that the extent of elevation in serum ADMA in streptozotocin-induced diabetic rats w

关 键 词：病理生理学 糖尿病 一氧化氮合酶抑制物 含量 

分 类 号：R587.1[医药卫生—内分泌]