低剂量的TGF-β1对早期糖尿病肾病模型的保护作用的研究
首发时间:2013-08-16
摘要:目的:研究低剂量的TGF-β1和/或IL-6受体α的单克隆抗体(抗-IL-6Rα)是否能在由链脲佐菌素(STZ)诱导的早期糖尿病肾病(DN)模型中通过重新平衡调节性T细胞(Treg细胞)/Th17细胞来延缓肾损伤和保护肾功能。方法:通过在C57BL / 6小鼠中少量多次注射STZ来诱发DN。采用低剂量的TGF-β1(0.1ug/小鼠/周)和/或抗IL-6Rα(10ug/小鼠/周)6次剂量给药,糖尿病发病40天后,测量代谢指标,肾脏结构,Treg/Th17平衡,和细胞因子mRNA表达等指标。结果:低剂量的TGF-β1并不会引起肾功能的损害,反而能降低血糖,改善肾脏肥大,并且在早期DN中诱导Treg/Th17平衡。而低剂量的TGF-β1+抗-IL-6Rα或单独的抗IL-6Rα不能保护DN。结论:这项研究表明,在早期DN中,低剂量TGF-β1能改善代谢紊乱和延缓肾功能损害,具有保护作用。
关键词: 调节性T细胞 糖尿病肾病 链脲佐菌素 Th17细胞 TGF-β1 IL-6阻断
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Protective Role of Low-dose TGF-β1 in Early Diabetic Nephropathy
Abstract:To determine whether low-dose TGF-β1 and/or IL-6-receptorα monoclonal antibody (anti-IL-6Rα) can be used to delay renal damage and preserve renal function by rebalancing regulatory T (Treg)/Th17 cells during the course of early diabetic nephropathy (DN) induced by streptozotocin (STZ). Diabetes was induced in C57BL/6 mice by multiple STZ injection. Low-dose TGF-β1 (0.1 μg/mouse/week) and/or anti-IL-6Rα (10 μg/mouse/week) were administered 6 dozes after STZ injection. After 40 days of diabetes onset, metabolic indices, renal structure, Treg/Th17 balance, and inflammatory cytokines' mRNA copies were assessed. Low-dose TGF-β1, instead of causing renal damage, decreased blood glucose, ameliorated kidney hypertrophy, and induced Treg/Th17 balance in early DN. Interestingly, low-dose TGF-β1 + anti-IL-6Rα or anti-IL-6Rα alone did not attenuate DN. This study provides experimental evidence of the protective effects of low-dose TGF-β1 in improving metabolic disorder and slowing renal damage in early DN.
Keywords: Diabetic nephropathy Regulatory T cells Streptozotocin Th17 cells TGF-β1 IL-6 blockade
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低剂量的TGF-β1对早期糖尿病肾病模型的保护作用的研究
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