Lambourne J E, Brown A M, Calcutt N, Tomlinson D R, Willars G B
Department of Physiology and Pharmacology, Medical School, University of Nottingham, UK.
Diabetologia. 1988 Jun;31(6):379-84. doi: 10.1007/BF02341507.
This study measured the ouabain-sensitive and ouabain-resistant adenosine triphosphatase activity in homogenates of the sciatic nerves and of pooled fourth and fifth lumbar dorsal root ganglia from rats fed 20% galactose or made diabetic with streptozotocin for either 4 or 8 weeks. Diabetes caused reductions in both fractions of sciatic nerve adenosine triphosphatase activity. After 8 weeks the ouabain-sensitive fraction was 54% of control (p less than 0.05) and the ouabain-resistant fraction was 57% of control (p less than 0.05). Galactose feeding more than doubled the ouabain-sensitive adenosine triphosphatase activity in the sciatic nerve (225% of control after 4 weeks, 215% of control after 8 weeks of galactose feeding, both p less than 0.01) and produced a progressive increase in the ouabain-resistant fraction (119% of control at 4 weeks (p less than 0.05) and 176% of control at 8 weeks (p less than 0.01)). In a group of rats fed galactose for 5 days, sciatic nerve ouabain-sensitive adenosine triphosphatase activity was 165% of control. Treatment with the aldose-reductase inhibitors tolrestat, ponalrestat or sorbinil prevented accumulation of polyol and depletion of myo-inositol in the sciatic nerves, indicating effective inhibition of aldose reductase. These drugs prevented completely the effect of galactose on the sciatic nerve adenosine triphosphatase activity, but had no significant effect on the reduction in adenosine triphosphatase activity in the sciatic nerves of diabetic rats. In the dorsal root ganglia galactose feeding had no measurable effect on the adenosine triphosphatase activity. Diabetes caused a modest numerical reduction in the ouabain-sensitive activity only.(ABSTRACT TRUNCATED AT 250 WORDS)
本研究测定了喂食20%半乳糖或用链脲佐菌素诱导糖尿病4周或8周的大鼠坐骨神经匀浆以及第四和第五腰段背根神经节匀浆中哇巴因敏感和哇巴因抗性的三磷酸腺苷酶活性。糖尿病导致坐骨神经三磷酸腺苷酶活性的两个部分均降低。8周后,哇巴因敏感部分为对照组的54%(p<0.05),哇巴因抗性部分为对照组的57%(p<0.05)。喂食半乳糖使坐骨神经中哇巴因敏感的三磷酸腺苷酶活性增加了一倍多(半乳糖喂养4周后为对照组的225%,8周后为对照组的215%,两者p<0.01),并使哇巴因抗性部分逐渐增加(4周时为对照组的119%(p<0.05),8周时为对照组的176%(p<0.01))。在一组喂食半乳糖5天的大鼠中,坐骨神经哇巴因敏感的三磷酸腺苷酶活性为对照组的165%。用醛糖还原酶抑制剂托瑞司他、泊那司他或索比尼尔治疗可防止坐骨神经中多元醇的积累和肌醇的消耗,表明醛糖还原酶受到有效抑制。这些药物完全阻止了半乳糖对坐骨神经三磷酸腺苷酶活性的影响,但对糖尿病大鼠坐骨神经中三磷酸腺苷酶活性的降低没有显著影响。在背根神经节中,喂食半乳糖对三磷酸腺苷酶活性没有可测量的影响。糖尿病仅使哇巴因敏感活性略有数值上的降低。(摘要截短于250字)