Qiang X, Satoh J, Sagara M, Fukuzawa M, Masuda T, Miyaguchi S, Takahashi K, Toyota T
Third Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Metabolism. 1998 Aug;47(8):977-81. doi: 10.1016/s0026-0495(98)90354-7.
N-acetylcysteine and pentoxifylline, free radical scavengers and inhibitors of tumor necrosis factor-alpha (TNF-alpha) production, inhibit the development of peripheral neuropathy in streptozotocin (STZ)-induced diabetic rats. This study was designed to elucidate the effect of gliclazide, an oral hypoglycemic sulfonylurea, on diabetic neuropathy, because it has been indicated to be a free radical scavenger and TNF-alpha inhibitor. Rats were fed with powder chow mixed with gliclazide or glibenclamide as a control ad libitum. Blood glucose levels and body weight were remarkably higher and lower in diabetic than in nondiabetic rats, respectively, while gliclazide and glibenclamide had no effect on these in both diabetic and nondiabetic rats throughout a 24-week experiment. Serum lipoperoxide levels and lipopolysaccharide (LPS)-induced serum TNF-alpha activities were significantly increased in diabetic rats, whereas these were significantly inhibited in gliclazide-treated rats. Motor nerve conduction velocity (MNCV) of the tibial nerve significantly slowed in diabetic rats compared with nondiabetic rats. On the other hand, the slowed MNCV was significantly inhibited in gliclazide-treated diabetic rats after 16 experimental weeks. Morphometric analysis showed that gliclazide prevented decreased myelinated fiber area (P < .05), increased fiber density (P < .001), and decreased axon/myelin ratio (P < .05) in diabetic rats. Glibenclamide treatment did not affect serum lipoperoxide, TNF-alpha, MNCV, or nerve morphology in this experiment. These results indicate that gliclazide has a beneficial effect on peripheral neuropathy in STZ-induced diabetic rats, irrespective of blood glucose levels.
N-乙酰半胱氨酸和己酮可可碱作为自由基清除剂以及肿瘤坏死因子-α（TNF-α）生成抑制剂，可抑制链脲佐菌素（STZ）诱导的糖尿病大鼠外周神经病变的发展。本研究旨在阐明口服降糖磺脲类药物格列齐特对糖尿病神经病变的影响，因为它已被证实是一种自由基清除剂和TNF-α抑制剂。给大鼠随意喂食混有格列齐特或作为对照的格列本脲的粉状饲料。在整个24周的实验中，糖尿病大鼠的血糖水平和体重分别显著高于和低于非糖尿病大鼠，而格列齐特和格列本脲对糖尿病和非糖尿病大鼠的这些指标均无影响。糖尿病大鼠的血清脂过氧化物水平和脂多糖（LPS）诱导的血清TNF-α活性显著升高，而在格列齐特治疗的大鼠中这些指标被显著抑制。与非糖尿病大鼠相比，糖尿病大鼠胫神经的运动神经传导速度（MNCV）显著减慢。另一方面，在16周实验后，格列齐特治疗的糖尿病大鼠减慢的MNCV被显著抑制。形态计量分析表明，格列齐特可防止糖尿病大鼠有髓纤维面积减少（P <.05）、纤维密度增加（P <.001）以及轴突/髓鞘比值降低（P <.05）。在本实验中，格列本脲治疗对血清脂过氧化物、TNF-α、MNCV或神经形态均无影响。这些结果表明，无论血糖水平如何，格列齐特对STZ诱导的糖尿病大鼠外周神经病变都有有益作用。
