Kamenov Z, Higashino H, Todorova M, Kajimoto N, Suzuki A
Department of Pharmacology, Kinki University School of Medicine, Osaka, Japan.
Methods Find Exp Clin Pharmacol. 2006 Jan-Feb;28(1):13-8. doi: 10.1358/mf.2006.28.1.962772.
Diabetic neuropathy is a very common complication of diabetes mellitus, and animal studies have contributed tremendously to its understanding. The aim of this study was to estimate the neuropathic alterations in the Otsuka Long-Evans Tokushima fatty (OLETF) rats, an animal model of human type 2 diabetes mellitus. For this purpose, four groups of animals were used: untreated OLETF rats, sucrose-fed for 2 months OLETF rats, untreated Long-Evans Tokushima Otsuka (LETO) nondiabetic rats as genetic controls of OLETF, and sucrose-fed LETO rats. All were examined at baseline, at the end of the sucrose treatment, and during a washout period. The following parameters were evaluated: motor nerve conduction velocity (MNCV), sensitivity to noxious thermal and mechanical stimuli using the tail-flick (TF) and tail-pressure (TP) tests, and blood glucose (BG) and HbA1c levels. Our results showed that BG and HbA1c were significantly higher in OLETF rats when compared with those in control LETO rats. Sucrose caused remarkable increase of BG and HbA1c in the OLETF rats, but not in the sucrose-fed LETO rats. MNCV and thermal nociception significantly decreased in OLETF rats in their 10th month, while the values of the TP test did not differ compared with those from LETO rats. Sucrose administration significantly decreased the MNCV, and increased the pain threshold evaluated by the TF and TP tests, compared with those in the control OLETF rats. The studied parameters were not significantly altered in sucrose-fed LETO rats. In conclusion, our findings show that signs of diabetic neuropathy appear late in the individual development of the OLETF rats, and MNCV and thermal nociception are selectively affected in this strain. Sucrose deteriorated the diabetic state, decreased MNCV, and caused thermal and mechanical hypoalgesia.
糖尿病性神经病变是糖尿病非常常见的并发症,动物研究对理解该疾病有巨大贡献。本研究的目的是评估大冢长-艾氏-德岛肥胖(OLETF)大鼠(一种人类2型糖尿病动物模型)的神经病变改变。为此,使用了四组动物:未经处理的OLETF大鼠、蔗糖喂养2个月的OLETF大鼠、作为OLETF基因对照的未经处理的长-艾氏-德岛大冢(LETO)非糖尿病大鼠以及蔗糖喂养的LETO大鼠。所有动物在基线、蔗糖处理结束时以及洗脱期进行检查。评估了以下参数:运动神经传导速度(MNCV)、使用甩尾(TF)和尾压(TP)试验对有害热刺激和机械刺激的敏感性,以及血糖(BG)和糖化血红蛋白(HbA1c)水平。我们的结果显示,与对照LETO大鼠相比,OLETF大鼠的BG和HbA1c显著更高。蔗糖使OLETF大鼠的BG和HbA1c显著升高,但在蔗糖喂养的LETO大鼠中未出现这种情况。OLETF大鼠在第10个月时MNCV和热痛觉显著降低,而TP试验的值与LETO大鼠相比无差异。与对照OLETF大鼠相比,蔗糖给药显著降低了MNCV,并提高了通过TF和TP试验评估的疼痛阈值。在蔗糖喂养的LETO大鼠中,所研究的参数没有显著改变。总之,我们的研究结果表明,糖尿病性神经病变的体征在OLETF大鼠个体发育后期出现,并且该品系中MNCV和热痛觉受到选择性影响。蔗糖使糖尿病状态恶化,降低了MNCV,并导致热和机械性痛觉减退。