FK506 ameliorates renal injury in early experimental diabetic rats induced by streptozotocin.
FK506 ameliorates renal injury in early experimental diabetic rats induced by streptozotocin.
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FK506 可改善链脲佐菌素诱导的早期实验性糖尿病大鼠的肾损伤。
DOI：
10.1016/j.intimp.2011.05.023
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发表时间：
2011
影响因子：
5.6
通讯作者：
Ji
中科院分区：
文献类型：
--
作者：
X. Qi;Yong;Chaochao Liang;Pei Zhang;Jing Dong;Kejun Ren;Wei Zhang;F. Fang;Ji
钙调神经磷酸酶（CaN）在早期糖尿病肾病肾小球肥大和细胞外基质积聚中起重要作用。环孢霉素（CSA），钙调神经抑制剂，已被证明可以减少链脲佐菌素诱导的糖尿病大鼠的肾损伤。本实验观察了免疫抑制作用为CSA 10-100倍的FK 506是否能抑制实验性糖尿病大鼠的糖尿病肾病进展。用链脲佐菌素（STZ）诱发大鼠糖尿病模型，每日1次口服FK 506（0.5或1.0mg/kg），连续4周。FK 506 1.0mg/kg可显著降低肾重（P<0.05），0.5和1.0mg/kg可显著降低24小时尿白蛋白排泄率（P<0.05，0.01）。FK 506 0.5和1.0mg/kg可显著降低肾小球体积（p<0.05），仅1.0mg/kg可改善肾小管间质损伤指数（p<0.01）。Western blot分析显示糖尿病大鼠肾脏CaN蛋白表达增加2.4倍，FK 506 0.5和1.0mg/kg可分别降低CaN蛋白表达38.0%和73.2%。FK 506治疗后，糖尿病大鼠肾组织1α（IV）胶原、p65、p-p65、OPN、α-SMA和TGF-β1蛋白表达明显减少（p<0.05，0.01）。FK 506对糖尿病大鼠早期肾损伤有一定的保护作用，其机制可能与抑制糖尿病大鼠肾组织CaN的增加有关。
Calcineurin (CaN) plays an important role in glomerular hypertrophy and extracellular matrix accumulation in early diabetic nephropathy. Cyclosporine (CSA), a CaN inhibitor, has been shown to reduce renal injury in streptozotocin-induced diabetic rats. We examined whether FK506, which immunosuppressive action was 10–100 times of CSA, inhibits progression of diabetic nephropathy in experimental diabetic rats. Diabetes was induced with streptozotocin in rats, and FK506 (0.5 or 1.0mg/kg) was orally administered once a day for 4weeks. Increased relative kidney weight was significantly reduced by FK506 treatment with 1.0mg/kg (p<0.05), and elevated 24hour urinary albumin excretion rate was markedly attenuated by FK506 treatment with 0.5 and 1.0mg/kg (p<0.05, 0.01). Elevated glomerular volume was significantly attenuated by FK506 treatment with 0.5 and 1.0mg/kg (p<0.05), and increased indices for tubulointerstitial injury were only ameliorated by FK506 treatment with 1.0mg/kg (p<0.01). Western blot analysis noted that the expression of CaN protein was increased 2.4 fold in the kidney from diabetic rats, and FK506 treatment with 0.5 and 1.0mg/kg could reduce increased expression of CaN protein by 38.0% and 73.2%. The expression of 1α (IV) collagen, p65, p-p65, OPN, α-SMA and TGF-β1 protein in kidney was significantly increased in diabetic rats and reduced by FK506 treatment (p<0.05, 0.01). Our results show that FK506 could ameliorate renal injury in early experimental diabetic rats, which mechanism may be at least partly correlated with suppression on increased CaN in renal tissue in diabetic rats.