Reactive oxygen species mediate abnormal contractile response to sympathetic nerve stimulation and noradrenaline in the vas deferens of chronically diabetic rats:: effects of in vivo treatment with antioxidants
Reactive oxygen species mediate abnormal contractile response to sympathetic nerve stimulation and noradrenaline in the vas deferens of chronically diabetic rats:: effects of in vivo treatment with antioxidants
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DOI：
10.1111/j.1472-8206.2004.00312.x
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发表时间：
2005-02-01
影响因子：
2.9
通讯作者：
Karasu, Ç
中科院分区：
文献类型：
--
作者：
Günes, A;Ceylan, A;Karasu, Ç
先前的研究表明，氧化应激增加与糖尿病神经病变之间存在联系。此外，抗氧化剂可以保护神经元免受活性氧的退化作用。在我们的研究中，我们用链脲佐菌素(STZ)-糖尿病大鼠建立了8个月的慢性糖尿病模型，研究了吡哆吲哚抗氧化剂斯托巴定（ST）和维生素E在体内治疗的效果。STZ-糖尿病大鼠在STZ注射后10天开始，通过口服导管给予ST （24.7 mg/kg/天）、维生素E （D， l - α -乙酸生育酚，400-500 IU/kg/天）或ST加维生素E治疗8个月。糖尿病大鼠的血糖和糖化血红蛋白水平分别升高了约400和100%。抗氧化处理显著降低血红蛋白糖基化（P < 0.05）。我们还通过测量离体输精管的收缩力来确定慢性糖尿病对交感神经传递的影响。此外，我们研究了电场刺激（EFS） （1-64 Hz）引起的收缩，与对照组大鼠相比，糖尿病大鼠的收缩明显减少。单独使用ST或维生素E治疗部分增强了EFS引起的收缩幅度，但ST和维生素E联合治疗没有显示出额外的效果。与对照组大鼠相比，糖尿病大鼠输精管对外源性去甲肾上腺素的收缩反应增加。虽然单独添加维生素E没有效果，但ST完全将去甲肾上腺素诱导的收缩恢复到基础水平。120 mM KCl诱导的张力在各实验组间无统计学差异。在正常大鼠中，自由基生成物邻苯三酚（10(-4)M）显著抑制了efs诱导的收缩。邻苯三酚对EFS （32 Hz）诱导的环切片收缩的抑制百分比为：对照组48 +/- 5.8，未治疗组75 +/- 5.5，st治疗组54 +/- 2.7，维生素e治疗组58 +/- 4.7。ST和维生素E联合治疗的效果与单独抗氧化剂相同，抑制率为48 +/- 6.8 %。这些结果与慢性糖尿病大鼠交感神经的退行性改变和功能异常一致，导致输尿管对肾上腺素能激动剂的反应减少和反应增加。此外，我们证明活性氧是糖尿病输精管交感神经传递受损和功能异常的原因，并且抗氧化剂的组合可能更好地治疗男性糖尿病患者的生殖系统残疾。
Previous studies suggest that a link exists between increased oxidative stress and diabetic neuropathy. Moreover, antioxidants may protect neurones from the degenerative effects of reactive oxygen species. In our study, we used streptozotocin (STZ)-diabetic rats in a 8-month chronic diabetes model to study the effects of in vivo treatment with stobadine (ST), a pyridoindole antioxidant, and vitamin E. STZ-diabetic rats were treated with ST (24.7 mg/kg/day), vitamin E (D,L-alpha-tocopheryl acetate, 400-500 IU/kg/day) or ST plus vitamin E through an intra-oral catheter for a 8-month period beginning 10 days after STZ injection. Blood glucose and HbA1c levels were increased in diabetic rats by about 400 and 100%, respectively. Antioxidant treatment significantly decreased haemoglobin glycosylation (P < 0.05). We also determined the effects of chronic diabetes on sympathetic neurotransmission by measuring the contractility of isolated vas deferens. Furthermore, we investigated contractions elicited by electrical field stimulation (EFS) (1-64 Hz) which were significantly decreased in diabetic rats when compared with control rats. Treatment with ST or vitamin E alone partly enhanced the amplitude of the contractions induced by EFS, but a combination of ST and vitamin E treatment showed no additional effects. Contractile response of the vas deferens to exogenous noradrenaline, was increased in diabetic rats when compared with control rats. While the addition of vitamin E alone had no effect, ST completely returned noradrenaline-induced contractions to basal levels. The tension induced by 120 mM KCl was not statistically different among the experimental groups. In normal rats, EFS-induced contractions were significantly inhibited by pyrogallol (10(-4) M), a free-radical generator. Percentage inhibition of pyrogallol on EFS (32 Hz)-induced contractions in ring sections was 48 +/- 5.8 in control, 75 +/- 5.5 in untreated-diabetic, 54 +/- 2.7 in ST-treated diabetic, and 58 +/- 4.7 in vitamin E-treated diabetic rats. Combining both ST and vitamin E treatment had the same effects as each antioxidant alone with a percent inhibition of 48 +/- 6.8. These results are consistent with the degenerative changes seen in sympathetic nerves and the abnormal function observed in chronically diabetic rats, leading to a decrease in EFS response and an increase in response to adrenergic agonists in the vas deferens. Furthermore, we demonstrated that reactive oxygen species are responsible for impaired sympathetic neurotransmission and abnormal function of diabetic vas deferens, and that a combination of antioxidants may be better for the therapy of reproductive system disabilities in male diabetics.