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生育三烯酚对实验性糖尿病神经病变中神经功能障碍、热痛觉过敏和氧化应激的影响。

Effects of trolox on nerve dysfunction, thermal hyperalgesia and oxidative stress in experimental diabetic neuropathy.

作者信息

Sharma Shyam S, Sayyed Sufyan G

机构信息

Molecular Neuropharmacology Laboratory, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Punjab, India.

出版信息

Clin Exp Pharmacol Physiol. 2006 Nov;33(11):1022-8. doi: 10.1111/j.1440-1681.2006.04481.x.

Abstract
  1. Diabetic neuropathy is one of the most common complications of diabetes and oxidative stress has been implicated to play a major role in its pathophysiology. 2. In the present study, we targeted oxidative stress using trolox, an anti-oxidant, in streptozotocin-induced diabetic neuropathy in rats. 3. Compared with control rats, diabetic rats showed significant deficits in motor nerve conduction velocity (MNCV; 49.91 +/- 1.94 vs 42.77 +/- 1.39 m/s, respectively) and nerve blood flow (NBF; 107.98 +/- 8.22 vs 38.9 +/- 2.7 arbitarary perfusion units, respectively) after 8 weeks of diabetes. Tail flick latencies for cold and hot immersion tests were also significantly reduced in diabetic rats, indicating thermal hyperalgesia. These observations indicate development of diabetic neuropathy. 4. A significant decrease in the activity of anti-oxidant enzymes (superoxide dismutase and catalase) and an increase in lipid peroxidation were observed in sciatic nerves from diabetic rats compared with age-matched control rats. Alterations in the activity of anti-oxidant enzymes and lipid peroxidation in diabetic rats indicate oxidative stress in diabetic neuropathy. 5. Two weeks treatment with trolox (10 and 30 mg/kg, i.p.) started on completion of the 6th week of diabetes significantly improved MNCV, NBF and inhibited thermal hyperalgesia. Trolox treatment also improved the activity of anti-oxidant enzymes and inhibited lipid peroxidation in sciatic nerves of diabetic rats. 6. The results of the present study suggest the beneficial effects of trolox in experimental diabetic neuropathy.
摘要
  1. 糖尿病性神经病变是糖尿病最常见的并发症之一,氧化应激被认为在其病理生理过程中起主要作用。2. 在本研究中,我们使用抗氧化剂曲洛司坦针对氧化应激,研究其对链脲佐菌素诱导的大鼠糖尿病性神经病变的影响。3. 与对照大鼠相比,糖尿病大鼠在糖尿病8周后运动神经传导速度(MNCV;分别为49.91±1.94与42.77±1.39 m/s)和神经血流量(NBF;分别为107.98±8.22与38.9±2.7任意灌注单位)显著降低。糖尿病大鼠冷热浸浴试验的甩尾潜伏期也显著缩短,表明存在热痛觉过敏。这些观察结果表明糖尿病性神经病变的发生。4. 与年龄匹配的对照大鼠相比,糖尿病大鼠坐骨神经中抗氧化酶(超氧化物歧化酶和过氧化氢酶)活性显著降低,脂质过氧化增加。糖尿病大鼠抗氧化酶活性和脂质过氧化的改变表明糖尿病性神经病变存在氧化应激。5. 糖尿病第6周结束后开始用曲洛司坦(10和30 mg/kg,腹腔注射)治疗两周,显著改善了MNCV、NBF并抑制了热痛觉过敏。曲洛司坦治疗还改善了糖尿病大鼠坐骨神经中抗氧化酶的活性并抑制了脂质过氧化。6. 本研究结果提示曲洛司坦对实验性糖尿病性神经病变具有有益作用。

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