环孢素对早期糖尿病肾病大鼠肾脏的保护作用

The reno-protective effects of cyclosporin A on early staged diabetic nephropathy in rats

目的研究环孢素(CsA)对实验性1型糖尿病大鼠早期肾脏损害的保护作用。方法将健康雄性Wistar大鼠分成3组,即单肾切除对照组24只,糖尿病(DM)组30只,糖尿病环孢素A治疗组30只,后两组每日注射中效胰岛素(NPH)1～4U,使血糖维持在11.1～22.2mmol/L,在糖尿病成模后每日管饲DM+CsA组大鼠CsA10mg/kg,其余两组管饲等量蒸馏水。分别于饲养2、4、8周后处死各组1/3量大鼠,检测肾重、血糖、内生肌酐清除率、24h尿白蛋白排泄率。结果DM组大鼠随着病程的延长肾重增加,内生肌酐清除率增高,并出现进行性微量白蛋白尿,与各时段对照组比较差异有统计学意义(P<0.05);而DM+CsA组大鼠肾重低于各时段DM组肾重,但差异无统计学意义(P>0.05),内生肌酐清除率8周时明显低于DM组[(4.5±0.7)ml/minvs(7.3±2.9)ml/min,P<0.05],24h尿白蛋白排泄率于2、4、8周时均低于DM组(P<0.05)。结论CsA对1型糖尿病大鼠早期肾脏损害有保护作用,其机制主要是通过抗炎、抗增殖作用产生。

Objeelive To investigate the reno-protective effects of Cyclosporin A on early-staged diabetic nephropathy in rats with artificial type 1 diabetes mellitus. Methods Adult male Wistar rats were unilaterally nephrectomized and allocated into three groups： the nephrectomy group （control group, n=24）, streptozotocin-induced diabetes group （DM group, n=30） and cyclosporin-treated DM group （DM＋CsA group, n=30）. The latter two groups received daily injection of 1-4 U NPH insulin to maintain the blood sugar between 11.1 -22.2 mmol/L. For the DM＋ CsA group, 10 mg/kg CsA was administered daily by gavage, while equivalent aliquots of distilled water were given to the other two groups. At weeks 2, 4 and 8, every one-thirds of rats from each group were sacrificed, and parameters of body weight, kidney weight, blood glucose, endogenous creatinine clearance rate （Ccr） and urine albumin excretion rate were collected. Results After 2, 4 and 8 weeks, the DM group developed progressive albuminuria, increasing kidney weight and significantly higher Ccr as compared with control group. At all time spots, lower kidney weight in DM＋CsA group compared with DM group, although statistically insignificant （P〉0.05）, was observed. Moreover, DM＋ CsA group presented with remarkably lower Ccr than in DM group after 8 weeks （4.5＋0.7 ml/min vs 7.3±2.9 ml/min, P〈 0.05）, and lower urine albumin excretion rates after 2, 4 and 8 weeks respectively （all P〈0.05）. Conclusion These finding are consistent with the notion that CsA may help prevent the progression of diabetic nephropathy by anti-inflammatory and anti-proliferating effects.