褪黑素对糖尿病周围神经病变大鼠氧化应激的作用

Inhibitory Effect of Melatonin on Oxidative Stress in Diabetic Peripheral Neuropathy Rats

研究褪黑素(melatonin,MEL)对糖尿病周围神经病变(diabetic peripheral neuropathy,DPN)大鼠氧化应激和神经功能及形态学的影响,并与抗氧化剂硫辛酸进行比较。链脲佐菌素诱导糖尿病(DM)大鼠模型,维持饲养8周后随机分为4组:DM对照组、褪黑素小剂量治疗组(0.5 mg.kg-1.d-1)、褪黑素大剂量治疗组(10mg.kg-1.d-1)、硫辛酸治疗组(100mg.kg-1.d-1)。造模前预设鼠龄和体重相当的正常对照组8只。MEL和硫辛酸干预治疗8周后检测各组大鼠血浆和坐骨神经抗氧化酶活性和胆质过氧化产物含量的变化,大鼠摆尾阈值、坐骨神经超微结构和神经传导速度的变化。结果显示,DM对照组大鼠血浆和坐骨神经中丙二醛(MDA)含量明显增加,超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性显著降低,摆尾阈值提高,坐骨神经传导速度降低,坐骨神经出现脱髓鞘以及轴突萎缩等病理变化。MEL和硫辛酸均可显著改善上述变化。DM时自由基的损伤和抗氧化能力的降低可能在DPN的发生发展中发挥重要作用。

To study the effect of melatonin on oxidative stress, sciatic nerve function and ultrastructure changes in diabetic rats and to compare antioxidation with antioxidant α-lipoic acid, models of diabetic rats were induced by streptozocin. Eight weeks later, diabetic peripheral neuropathy models were divided into4 groups： （1）DM; （2）MEL1（0. 5mg· kg^-1 · d^-1）; （3） MEL2（10mg · kg^-1 · d^-1）, （4） LA（100mg · kg^-1 · d^-1）. Eight normal rats served as normal control （NC） group. Eight weeks later, plasma and sciatic nerve antioxidant enzymes activities, lipid peroxide product levels, sciatic nerve ultrastructure changes and nerve conduction velocities, tailflick threshold were evaluated. Results showed that MEL and α-lipoic acid increased superoxide dismutase and glutathione peroxidase activities and reduced, malonaldehyde levels in sciatic nerve and plasma, meliorated tailflick threshold, sciatic nerves nerve conduction velocities and ultrastructure changes. Overproduction of reactive oxygen free radicals and insufficieny in antioxidant enzymes may contribute to development of diabetic peripheral neuropathy.