Triptolide markedly attenuates albuminuria and podocyte injury in an animal model of diabetic nephropathy.

Triptolide markedly attenuates albuminuria and podocyte injury in an animal model of diabetic nephropathy.
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雷公藤甲素可显着减轻糖尿病肾病动物模型中的蛋白尿和足细胞损伤。

DOI:
10.3892/etm.2013.1226
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发表时间:
2013-09
影响因子:
2.7
通讯作者:
Xu L
Xu L
中科院分区:
医学4区
文献类型:
--
作者:
Ma R;Liu L;Liu X;Wang Y;Jiang W;Xu L

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雷公藤内酯醇是雷公藤的主要活性成分,具有显著的免疫抑制、抗炎和足细胞保护作用。在这项研究中,雷公藤内酯醇抑制炎症和减轻足细胞损伤的能力,在糖尿病肾病(DN)大鼠模型进行了检查。用雷公藤内酯醇治疗伴有DN的II型糖尿病大鼠,剂量为100 μ g. kg-1. day-1。雷公藤内酯醇治疗8周后,评估尿白蛋白水平、肾重/体重和肾脏中艾德-1(大鼠单核巨噬细胞的标志物)阳性细胞数。采用定量聚合酶链反应(qPCR)、免疫印迹和免疫组化分析雷公藤甲素对足细胞损伤和慢性炎症的影响。雷公藤内酯醇治疗后,II型糖尿病大鼠的蛋白尿明显减少。此外,肾小球肥大和足突消失得到改善,并且与nephrin和podocin表达相关的裂隔膜恢复。肾脏炎症也减轻。雷公藤内酯醇还能显著降低转化生长因子-β1和骨桥蛋白的表达以及艾德-1阳性细胞向肾脏的浸润。结果表明,雷公藤甲素能明显减轻DN大鼠蛋白尿和足细胞损伤,其机制可能与抑制炎症反应和巨噬细胞浸润有关。
Triptolide is a major active component of Tripterygium wilfordii Hook F, which exerts marked immunosuppressive, anti-inflammatory and podocyte-protective effects. In this study, the ability of triptolide to inhibit inflammation and attenuate podocyte injury was examined in a rat model of diabetic nephropathy (DN). Type II diabetic rats with DN were treated with triptolide at a dose of 100 μg.kg−1.day−1. Following 8 weeks of triptolide treatment, the urine albumin level, kidney weight/body weight and the number of cells positive for ED-1 (a marker for rat mononuclear macrophages) in the kidney were assessed. The effects of triptolide on podocyte injury and chronic inflammation were analyzed using quantitative polymerase chain reaction (qPCR), western blotting and immunohistochemistry. Following triptolide treatment, the albuminuria in the type II diabetic rats was significantly reduced. Furthermore, the glomerular hypertrophy and foot process effacement were improved, and there was a recovery of the slit diaphragm associated with nephrin and podocin expression. The inflammation in the kidneys was also attenuated. Furthermore, triptolide significantly reduced the expression of transforming growth factor-β1 and osteopontin, and the infiltration of ED-1-positive cells into the kidney. The results demonstrated that triptolide markedly attenuated albuminuria and podocyte injury in the rat model of DN, which may have been correlated with the inhibition of inflammation and macrophage infiltration in the kidneys.
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