Saini A K, Arun K H S, Kaul C L, Sharma S S
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S. Nagar, Mohali, Punjab 160 062, India.
Pharmacol Res. 2004 Dec;50(6):593-9. doi: 10.1016/j.phrs.2004.04.004.
Hyperglycemia is implicated to play a major role in development of diabetic neuropathy. Since most of the diabetics are hyperglycemic much before they develop full-blown diabetes, we felt, it would be very important to know the effects of acute hyperglycemia on nerve function so that early pathophysiological events could be understood and appropriate therapeutic intervention can be made. Moreover, effect of acute hyperglycemia on motor nerve conduction velocity (MNCV) and nerve blood flow (NBF) is not known. Hence, we studied the effects of acute hyperglycemia on sciatic MNCV and sciatic NBF in healthy male Sprague-Dawley (SD) rats. Three different animal models of acute hyperglycemia (50% glucose (3 g kg(-1), i.v. (intra-venous) or i.p. (intra-peritoneally)) or 24 h post-streptozotocin (STZ) injected rats were used. Acute hyperglycemia but not mannitol or sucrose significantly attenuated MNCV and NBF. Adenosine (10 mg kg(-1), i.p.) prevented the acute hyperglycemia-induced attenuation of MNCV and NBF in all the three rat models of acute hyperglycemia. Adenosine effects were blocked by theophylline (50 mg kg(-1), i.p.) suggesting the role of adenosinergic receptor mediated mechanisms in acute hyperglycemia-induced neuropathy. Acute glucose administration in 8 weeks, STZ diabetic rats did not further affect MNCV or NBF. Adenosine (10 mg kg(-1), i.p.) did not produce any adverse effects on the blood pressure and heart rate. From the results, we conclude that acute hyperglycemia attenuates MNCV and NBF via an adenosinergic receptor-dependent mechanism.
高血糖被认为在糖尿病神经病变的发展中起主要作用。由于大多数糖尿病患者在发展为全面糖尿病之前就已经处于高血糖状态很久了，我们认为，了解急性高血糖对神经功能的影响非常重要，这样可以理解早期病理生理事件并进行适当的治疗干预。此外，急性高血糖对运动神经传导速度（MNCV）和神经血流（NBF）的影响尚不清楚。因此，我们研究了急性高血糖对健康雄性Sprague-Dawley（SD）大鼠坐骨神经MNCV和坐骨神经NBF的影响。使用了三种不同的急性高血糖动物模型（50%葡萄糖（3 g kg(-1)，静脉注射或腹腔注射）或链脲佐菌素（STZ）注射后24小时的大鼠）。急性高血糖而非甘露醇或蔗糖显著降低了MNCV和NBF。腺苷（10 mg kg(-1)，腹腔注射）在所有三种急性高血糖大鼠模型中均预防了急性高血糖诱导的MNCV和NBF降低。茶碱（50 mg kg(-1)，腹腔注射）阻断了腺苷的作用，表明腺苷能受体介导的机制在急性高血糖诱导的神经病变中起作用。在8周龄的STZ糖尿病大鼠中急性给予葡萄糖并未进一步影响MNCV或NBF。腺苷（10 mg kg(-1)，腹腔注射）对血压和心率没有产生任何不良影响。从结果来看，我们得出结论，急性高血糖通过腺苷能受体依赖性机制降低MNCV和NBF。
