Rösen P, Ballhausen T, Bloch W, Addicks K
Department of Clinical Biochemistry, Diabetes Research Institute, Düsseldorf, Germany.
Diabetologia. 1995 Oct;38(10):1157-68. doi: 10.1007/BF00422364.
Increased oxidative stress has been suggested to contribute to disturbances in the regulation of coronary flow and the increased cardiac risk in diabetes mellitus. Using the isolated perfused heart of streptozotocin-diabetic rats our study shows that basal and maximal coronary flow (tested by infusion of sodium nitroprusside) are not altered in diabetes, but that 5-hydroxytryptamine (5-HT) stimulated endothelium-dependent increase in coronary flow becomes progressively impaired. This defect of the endothelium-dependent vasodilatation was prevented by perfusion of the hearts with superoxide dismutase and pretreatment of the diabetic rats with tocopherol-acetate. Morphological studies also revealed that pretreatment with tocopherol-acetate was cardioprotective, and largely prevented severe alterations of myocardial structure typically observed after a diabetes duration of 3 months; deterioration and fragmentation of myofilament bundles were seen less, and the numbers of areas of focal necrosis and of contraction bands were clearly reduced. In contrast to untreated diabetic hearts the autonomic nerve fibers detected by catecholamine fluorescence were running in parallel in hearts of tocopherol-treated diabetic rats, and the amount of catecholamines was not different from that of healthy control rats. Trichrome staining and immunohistochemical staining of collagen I and III showed a dramatic increase in number and the size of deposits of collagen fibers at precapillary locations in the diabetic hearts which were significantly reduced by anti-oxidative treatment. These findings demonstrate that oxidative stress may not only play a major role in the impairment of endothelium-dependent regulation of coronary flow, but also in the development of perivascular fibrosis and severe changes of the autonomic nerves and contractile system in myocardium.
氧化应激增加被认为与糖尿病患者冠状动脉血流调节紊乱及心脏风险增加有关。利用链脲佐菌素诱导的糖尿病大鼠的离体灌注心脏，我们的研究表明，糖尿病状态下基础和最大冠状动脉血流（通过硝普钠输注检测）未发生改变，但5-羟色胺（5-HT）刺激的内皮依赖性冠状动脉血流增加逐渐受损。用超氧化物歧化酶灌注心脏以及用醋酸生育酚预处理糖尿病大鼠可预防内皮依赖性血管舒张的这一缺陷。形态学研究还显示，用醋酸生育酚预处理具有心脏保护作用，很大程度上预防了糖尿病病程3个月后通常观察到的心肌结构严重改变；肌丝束的退化和断裂较少见，局灶性坏死区域和收缩带的数量明显减少。与未治疗的糖尿病心脏不同，通过儿茶酚胺荧光检测到的自主神经纤维在经生育酚处理的糖尿病大鼠心脏中平行排列，儿茶酚胺含量与健康对照大鼠无异。三色染色以及I型和III型胶原蛋白的免疫组化染色显示，糖尿病心脏毛细血管前位置的胶原纤维沉积物数量和大小显著增加，抗氧化治疗可使其明显减少。这些发现表明，氧化应激不仅可能在冠状动脉血流内皮依赖性调节受损中起主要作用，还可能在血管周围纤维化的发展以及心肌自主神经和收缩系统的严重变化中起主要作用。
