中文摘要：

目的探讨吡咯烷二硫代氨基甲酸盐（PDTC）对糖尿病大鼠血管内皮依赖性舒张功能损害的保护作用及其机制。方法雄性SD大鼠一次性ip给予链脲佐菌素60 mg·kg^-1制备糖尿病模型,通过饮水中给予PDTC 10 mg·kg^-1,连续治疗8周。检测血糖、血脂和血清内源性一氧化氮合酶（NOS）抑制物非对称性二甲基精氨酸（ADMA）浓度。用含有人二甲基精氨酸二甲胺水解酶2（h DDAH2）基因的重组腺病毒（Ad5CMV-h DDAH2）体外感染糖尿病大鼠血管环,分别检测感染前后血管环对乙酰胆碱诱导的最大舒张反应（Emax）、半数有效量（EC50）及血管组织DDAH活性。结果与正常组比较,糖尿病大鼠血糖明显升高,血清ADMA浓度从正常组的（1.14±0.26）μmol·L-1升至（2.18±0.52）μmol·L-1（P〈0.01）;血管组织DDAH活性也从正常组的（0.10±0.02）U·g-1蛋白降至（0.05±0.01）U·g-1蛋白（P〈0.01）;血管内皮依赖性舒张功能损伤,表现为Emax由正常组的（93.6±4.4）%降至（50.8±4.9）%（P〈0.01）,EC50由正常组的（88±22）nmol·L-1升至（240±45）nmol·L-1（P〈0.01）。PDTC治疗降低血糖和血清ADMA浓度分别至（13.2±3.5）mmol·L-1和（1.40±0.25）μmol·L-1（P〈0.01）,增加血管DDAH活性至（0.08±0.02）U·g-1蛋白（P〈0.01）,改善内皮依赖性血管舒张功能,使Emax增至（84.6±4.5）%,EC50降至（134±27）nmol·L-1（P〈0.01）。糖尿病大鼠血管转染DDAH2基因后,血管DDAH活性及Emax和EC50的变化与PDTC治疗组相似。结论 PDTC对糖尿病大鼠血管内皮依赖性舒张功能具有明显的保护作用,其机制可能与上调血管DDAH活性,降低内源性NOS抑制物ADMA蓄积有关。

英文摘要：

OBJECTIVE To investigate the protective effects and mechanisms of pyrrolidine dithio- carbamate （PDTC） against the impairment of endothelium-dependent vasodilation function in diabetic rats. METHODS A diabetic model was induced by a single intraperitoneal injection of streptozotocin （STZ, 60 mg· kg^-1） to male SD rats. Some of the diabetic rats were treated with PDTC （ 10 mg·kg^-1o d^-1） added to drinking water for 8 weeks after diabetes was induced. The levels of blood glucose, serum lip- id profiles and endogenous nitric oxide synthase （NOS） inhibitor asymmetric dimethylarginine dimethylarginine dimethylaminohydrolase 2 （DDAH2） gene adenovirus（Ad5CMV-hDDAH2）was ex vivo transfected to diabetic aortic rings. RESULTS The diabetic rats displayed a significant increase in blood glucose levels compared to normal control group. Serum ADMA levels were elevated from （1.14±0.26）μmol· L^-1 to （2.18±0.52）μmol· L^-1 （P〈0.01）, while vascular DDAH activity was decreased from （0.10±0.02）U· g^-1 protein to （0.05±0.01）U· g^-1 protein （P〈0.01） in diabetic rats compared with normal control group, respectively. The endothelium-dependent relaxation response to acetylcholine was significantly impaired, as expressed by the decreased Emax from （93.6±4.4）% to （50.8±4.9）% and increased ECso from （88±22）nmol·L^-1 to （240±45）nmo1· L^-1（P〈0.01） in diabetic rats compared to control group. Treatment with PDTC not only decreased the blood glucose level [ （13.2±3.5）mmol· L^-1） and serum ADMA concentration （1.40±0.25μmol·L^-1, P〈0.01） but also increased vascular DDAH activity E （0.08±0.02）U ·g^-1 protein, P〈0.01 ）] and endothelium-dependent relaxation, as expressed by a higher Emax （84.6±4.5）%（P〈0.01） and lower ECso （134±27）nmo1· L^-1 （P〈0.01） in diabetic rats. Similar results of Era,x, ECs0 and DDAH activity could also be observed when hDDAH2 gene was ex vivo trans- ferred to isolated aortic rings from di