Thomson K J, Saunders N J, Simpson J G, Whiting P H
Department of Pathology, University of Aberdeen, UK.
Br J Exp Pathol. 1989 Aug;70(4):405-14.
The effect of cyclosporin A (CsA), administered daily by gavage at 20 mg/kg body weight, on renal structure and function was investigated in normal and streptozotocin-diabetic male adult Sprague-Dawley rats over 12 weeks. In the non-diabetic animals CsA caused a progressive decrease in glomerular filtration rate and increased enzymuria. In contrast, the diabetic state was associated with massive increases in both enzymuria and urine flow rates, but a trend towards increased urea and creatinine clearance rates. CsA treatment of diabetic animals did not significantly alter the above parameters, nor affect circulating glucose levels, and trough serum CsA concentrations were similar in both diabetic and non-diabetic animals. The kidneys from CsA-treated non-diabetic animals showed chronic tubular damage. In the streptozotocin groups, the only morphological abnormality which could be related to diabetes was excess glycogen deposition in distal renal tubules. CsA-treatment of these groups was not associated with structural enhancement of either the drug's nephrotoxicity or the diabetes-related changes. Indeed the results indicate that the diabetic state affords some protection against the functional aspects of CsA-nephrotoxicity.
在12周的时间里，研究了以20毫克/千克体重每日经口灌胃给予环孢素A（CsA）对正常和链脲佐菌素诱导的糖尿病成年雄性Sprague-Dawley大鼠肾脏结构和功能的影响。在非糖尿病动物中，CsA导致肾小球滤过率逐渐降低，并增加酶尿。相反，糖尿病状态与酶尿和尿流率大幅增加相关，但尿素和肌酐清除率有增加趋势。用CsA治疗糖尿病动物并未显著改变上述参数，也未影响循环血糖水平，糖尿病和非糖尿病动物的谷值血清CsA浓度相似。经CsA治疗的非糖尿病动物的肾脏显示出慢性肾小管损伤。在链脲佐菌素组中，唯一与糖尿病相关的形态学异常是远端肾小管中糖原沉积过多。对这些组用CsA治疗与药物肾毒性或糖尿病相关变化的结构增强无关。事实上，结果表明糖尿病状态对CsA肾毒性的功能方面提供了一定的保护作用。
