Qiang X, Satoh J, Sagara M, Fukuzawa M, Masuda T, Sakata Y, Muto G, Muto Y, Takahashi K, Toyota T
Third Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Diabetologia. 1998 Nov;41(11):1321-6. doi: 10.1007/s001250051072.
Free-radical scavengers and inhibitors of tumour necrosis factor-alpha (TNF-alpha) such as N-acetylcysteine and pentoxifylline have been shown to inhibit the development of peripheral neuropathy in streptozotocin(STZ)-induced diabetic rats. In this study we examined the effect of troglitazone, an anti-diabetic thiazolidinedione, on diabetic neuropathy, since it also is a free-radical scavenger and a TNF-alpha inhibitor. Rats were fed powder chow mixed with troglitazone at 0.5% and 0.125% ad libitum. Although blood glucose concentrations were remarkably higher and body weight lower in diabetic than in nondiabetic rats, troglitazone had no effect on these throughout the 24-week experiment. Serum lipoperoxide concentrations, tibial nerve lipoperoxide content and serum TNF-alpha activity induced by lipopolysaccharide was increased in diabetic rats, but inhibited in troglitazone-treated rats. Motor nerve conduction velocity (MNCV) of the tibial nerve slowed in diabetic rats, compared with that in nondiabetic rats. On the other hand, the slowed MNCV was (p < 0.05-0.01) inhibited after weeks 12 and 16 of the experiment in diabetic rats treated with high and low doses of troglitazone, respectively. Morphometric analysis showed that troglitazone suppressed the decrease of the myelinated fibre area (p < 0.05), axon/myelin ratio (p < 0.01) and fascicular area (p < 0.05) and suppressed the increase of myelinated fibre density (p < 0.001) in diabetic rats. These results indicate that troglitazone has a beneficial effect on peripheral neuropathy in STZ-induced diabetic rats irrespective of blood glucose concentrations.
自由基清除剂以及肿瘤坏死因子-α（TNF-α）抑制剂，如N-乙酰半胱氨酸和己酮可可碱，已被证明可抑制链脲佐菌素（STZ）诱导的糖尿病大鼠周围神经病变的发展。在本研究中，我们研究了抗糖尿病噻唑烷二酮类药物曲格列酮对糖尿病神经病变的影响，因为它也是一种自由基清除剂和TNF-α抑制剂。给大鼠随意喂食含0.5%和0.125%曲格列酮的混合粉末饲料。尽管糖尿病大鼠的血糖浓度显著高于非糖尿病大鼠，体重低于非糖尿病大鼠，但在整个24周的实验中，曲格列酮对这些指标没有影响。糖尿病大鼠血清脂质过氧化物浓度、胫神经脂质过氧化物含量以及脂多糖诱导的血清TNF-α活性均升高，但曲格列酮治疗的大鼠中这些指标受到抑制。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）减慢。另一方面，在实验第12周和16周后，分别用高剂量和低剂量曲格列酮治疗的糖尿病大鼠中，减慢的MNCV受到抑制（p<0.05 - 0.01）。形态计量分析表明，曲格列酮抑制了糖尿病大鼠有髓纤维面积（p<0.05）、轴突/髓鞘比（p<0.01）和束状面积（p<0.05）的减少，并抑制了有髓纤维密度的增加（p<0.001）。这些结果表明，无论血糖浓度如何，曲格列酮对STZ诱导的糖尿病大鼠周围神经病变都有有益作用。
