Keegan A, Cotter M A, Cameron N E
Department of Biomedical Sciences, University of Aberdeen, Foresterhill, Scotland, United Kingdom.
Free Radic Biol Med. 1999 Sep;27(5-6):536-43. doi: 10.1016/s0891-5849(99)00125-2.
Transition-metal catalyzed reactions contribute to oxidative stress, which has been implicated in the pathogenesis of diabetic complications. The aim was to evaluate the effects of treatment with the transition metal chelator trientine on endothelium-dependent relaxation of aorta and corpus cavernosum from streptozotocin-induced diabetes of 8 weeks duration in rats. Effects on cavernosum autonomic innervation were also examined. Diabetes caused a 30.1 +/- 3.8% reduction in maximum aorta endothelium-dependent relaxation to acetylcholine (ACh), which was markedly attenuated (72.7 +/- 10.6%) by trientine treatment. Reversal treatment (4 weeks untreated diabetes, 4 weeks trientine) did not effect endothelium-dependent relaxation compared with aortas from rats with 4 weeks of diabetes, however, there was a 22.5 +/- 6.2% improvement compared with 8 weeks of diabetes. Eight weeks of diabetes caused a 41.5 +/- 6.6% reduction in corpus cavernosum endothelium-dependent maximum relaxation to ACh that was 70.1 +/- 16.9% prevented by trientine. Cavernosum nonadrenergic, noncholinergic (NANC) nerve stimulation caused frequency-dependent relaxation to a maximum of 40.9 +/- 2.4%, which was reduced by diabetes to 24.2 +/- 2.1%. Trientine partially prevented this deficit, maximum relaxation being 31.9 +/- 2.3%. Thus, metal chelator treatment has beneficial effects on aorta and cavernosum endothelium-dependent relaxation and on cavernosum NANC innervation.
过渡金属催化反应会导致氧化应激,而氧化应激与糖尿病并发症的发病机制有关。本研究旨在评估过渡金属螯合剂曲恩汀对大鼠链脲佐菌素诱导的8周糖尿病模型主动脉和海绵体内皮依赖性舒张功能的影响。同时也检测了其对海绵体自主神经支配的影响。糖尿病导致主动脉对乙酰胆碱(ACh)的最大内皮依赖性舒张功能降低30.1±3.8%,而曲恩汀治疗可显著减轻这种降低(72.7±10.6%)。与糖尿病4周的大鼠主动脉相比,逆转治疗(4周未治疗糖尿病,4周曲恩汀)对内皮依赖性舒张功能无影响,但与糖尿病8周的大鼠相比,有22.5±6.2%的改善。糖尿病8周导致海绵体对ACh的最大内皮依赖性舒张功能降低41.5±6.6%,曲恩汀可预防70.1±16.9%。海绵体非肾上腺素能、非胆碱能(NANC)神经刺激引起频率依赖性舒张,最大舒张率为40.9±2.4%,糖尿病使其降低至24.2±2.1%。曲恩汀部分预防了这种缺陷,最大舒张率为31.9±2.3%。因此,金属螯合剂治疗对主动脉和海绵体内皮依赖性舒张功能以及海绵体NANC神经支配具有有益作用。