Hotta N, Koh N, Sakakibara F, Nakamura J, Hamada Y, Naruse K, Sasaki H, Mizuno K, Matsubara A, Kakuta H
Third Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Exp Physiol. 1995 Nov;80(6):981-9. doi: 10.1113/expphysiol.1995.sp003909.
To determine the effect of an aldose reductase inhibitor, SNK-860, on the worsening of the electroretinogram (ERG) during a diabetic state, rats with streptozotocin-induced diabetes were administered SNK-860 (1 or 4 mg kg-1 orally) daily for 4 weeks. The effectiveness of SNK-860 in prolonging the peak latencies of oscillatory potentials in the b-wave of the electroretinogram of diabetic rats varied between these different waveform components (designated O1, O2 and O3). SNK-860 (4 mg kg-1 day-1) either completely or partially prevented the prolonged peak latencies at O1 and sigma(O1 + O2 + O3). The drug failed to shorten the latency of the O2 and O3 components, and produced only a modest reduction in retinal levels of sorbitol and fructose, with no increase in myo-inositol. There was a significant correlation between the state of the ERG (components O1 and sigma(O1 + O2 + O3)) and the retinal levels of sorbitol and fructose (P < 0.01), but not of myo-inositol. It is concluded that a better understanding of the mechanism by which SNK-860 acts may provide new insight into the pathogenesis of hyperglycaemic retinal dysfunction and help to establish effective therapy for diabetic retinopathy.
为了确定醛糖还原酶抑制剂SNK - 860对糖尿病状态下视网膜电图(ERG)恶化的影响,给链脲佐菌素诱导的糖尿病大鼠每日口服SNK - 860(1或4毫克/千克),持续4周。SNK - 860对延长糖尿病大鼠视网膜电图b波中振荡电位的峰值潜伏期的有效性在这些不同的波形成分(指定为O1、O2和O3)之间有所不同。SNK - 860(4毫克/千克/天)完全或部分预防了O1以及σ(O1 + O2 + O3)处延长的峰值潜伏期。该药物未能缩短O2和O3成分的潜伏期,并且仅使视网膜中山梨醇和果糖水平适度降低,而肌醇没有增加。ERG状态(成分O1和σ(O1 + O2 + O3))与视网膜中山梨醇和果糖水平之间存在显著相关性(P < 0.01),但与肌醇水平无关。得出的结论是,更好地理解SNK - 860的作用机制可能为高血糖性视网膜功能障碍的发病机制提供新的见解,并有助于建立糖尿病视网膜病变的有效治疗方法。