吡咯烷二硫代氨基甲酸盐对糖尿病大鼠血管内皮功能不全的影响及其机制
发布时间：2018-06-01 05:15
本文选题：糖尿病 + 内皮 ； 参考：《中国药理学与毒理学杂志》2015年04期
【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(P0.01);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(P0.01);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)%(P0.01),EC50由正常组的(88±22)nmol·L-1升至(240±45)nmol·L-1(P0.01)。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(P0.01),增加血管DDAH活性至(0.08±0.02)U·g-1蛋白(P0.01),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(P0.01)。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。
[Abstract]:Objective to investigate the protective effect and mechanism of pyrrolidine dithiocarbamate (PDTC) on vascular endothelium-dependent diastolic dysfunction in diabetic rats. Methods male Sprague-Dawley rats were given streptozotocin 60 mg kg-1 once by IP for 8 weeks. The diabetic model was treated with PDTC 10 mg kg -1 in drinking water for 8 weeks. Blood glucose, blood lipids and serum endogenous nitric oxide synthase (NOS) inhibitor, asymmetric dimethyl arginine (ADMA), were measured. The vascular rings of diabetic rats were infected with recombinant adenovirus Ad5CMV-h DDAH2 containing the human dimethyl arginine dimethylamine hydrolase 2hDDAH2 gene in vitro. The maximal diastolic response to acetylcholine induced by acetylcholine was measured before and after infection, and the activity of DDAH in vascular tissue was measured. Results compared with the normal group, the blood glucose of diabetic rats was significantly increased, the serum ADMA concentration was increased from 1.14 卤0.26 渭 mol L-1 to 2.18 卤0.52 渭 mol L-1 P0.01A, the DDAH activity of vascular tissue decreased from 0.10 卤0.02U g -1 protein to 0.05 卤0.01U g -1 protein P0.01a, and the vascular endothelium-dependent diastolic function was damaged. 琛ㄧ幇涓篍max鐢辨甯哥粍鐨，
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