【摘要】 目的:探讨链尿佐菌素（STZ）诱导的早期糖尿病C57BL（?）6J小鼠胸主动脉内皮依赖性舒张增强机制。方法:采用放免法测定糖尿病（DM）和对照（Control）组小鼠血清中前列环素（PGI₂）代谢物6-酮-前列环素F_（?）a(6-keto-PGF_1a)的含量,同时比较各组小鼠离体胸主动脉环对血管收缩剂、舒张剂的张力变化以及苯肾上腺素（PE）诱导的离体胸主动脉节律活动对各种阴断剂的反应性变化。结果:DM组小鼠血清6-ketoPGF_1a的含量较Control组显著增强[（1.8±1.0）μg/1.vs（0.5±0.3）μg/L,P<0.01];PE能够诱导DM和Control组小鼠离体胸主动脉环的节律活动,而且DM组的胸主动脉环节律活动振幅显著增大[（4.9±1.7）％vs（12±5）％,P<0.01]。DM组胸主动脉环对收缩剂PE和KCl 60 mmol/L的反应性比Control组显著增强;对内皮依赖性舒张剂乙酰胆碱（ACh）的反应也比Control组显著增强[（56±10）（?）vs（81±8）％,P<0.01].一氯化氮合酶抑制剂（L-NAME）和鸟苷酸环化酶抑制剂（LY-83583）分别能完全阴断Control组的PE诱导的节律活动和ACh的舒张效应,而在DM组只能部分阻断。L-NAME和吲哚美辛联用可以显著减小节律活动振幅和ACh的舒张效应（P<0.01）。钙激活型钾通道阻断剂（TEA）可以阻断内皮依赖性舒张因子（EDHF）的效应,它与L-NAME联用可以完全阻断节律活动?更多还原

【Abstract】 AIM: To investigate the mechanism of the enhanced endothelium-dependent vasodilatation in thoracic aorta of the early stage streptozotocin（STZ）-induced diabetic C57BL/6J mice. METHODS: Radioimmunity was used to detect the metabolite of prostaglandin Ⅰ₂ （PGI₂）, 6-keto-prostaglandin F_1α (6-keto-PGF_1α), in the blood serum. Vascular muscle tension and phenylephrine（PE）-induced rhythmic activity in the isolated thoracic aorta of mice were also compared. RESULTS: 6-Keto-PGF_1α in the serum was significantly higher in STZ-induced diabetic mice than age-matched controls[（1.8+1.0） μg/L vs（0.5±0.3）μg/L, P<0.01]. PE induced rhythmic activity in both diabetic and control mouse aorta but the amplitude was markedly higher in diabetic mice than in controls[（4.9±1.7）% vs （12±5） %, P<0.01]. PE, high K⁺ solution-induced contraction, and acetylcholine（ACh）-induced relaxation [（56±10）% vs （81±8）%, P<0.01] were notablely enhanced in diabetic mice than those in controls. Alone N^G-nitro-Larginine methyl ester （L-NAME） or 6-（phenylamino）-5,8-quinolinedione （LY-83583） abolished the rhythmic activity and ACh-induced relaxation in controls but only partially inhibited them in diabetic mice. Indomethacin did not affect rhythmic activity but depressed ACh-induced relaxation. L-NAME plus indomethacin significantly depressed the rhythmic activity and ACh-induced relaxation than L-NAME alone （P<0.01）. Furthermore tetraethylammonium plus L-NAME abolished them in diabetic mice. CONCLUSION: The mechanism that enhanced endotheliumdependent vasodilatation in STZ-induced diabetic mice is due to enhanced production of PGI₂ and endotheliumderived hyperpolarizing factor（EDHF）. The phenomena maybe only take place in early stage of diabetic mice.更多还原