Arctigenin suppresses renal interstitial fibrosis in a rat model of obstructive nephropathy
Arctigenin suppresses renal interstitial fibrosis in a rat model of obstructive nephropathy
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DOI：
10.1016/j.phymed.2017.03.003
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发表时间：
2017-07-01
期刊：
影响因子：
7.9
通讯作者：
Wang, Yitao
中科院分区：
文献类型：
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作者：
Li, Ao;Zhang, Xiaoxun;Wang, Yitao
工作背景：肾小管间质纤维化（TIF）通常是各种进行性损伤的最终结果，并导致终末期肾病。有几个治疗剂目前可用于延缓肾TIF.Purpose的发展：本研究的目的是评估牛蒡苷元（ATG），木脂素成分来自干牛蒡（牛蒡L.）的作用。方法：建立单侧输尿管梗阻（UUO）大鼠模型，分别给予溶剂、氨丁三醇（1和3 mg/kg/d）和氯沙坦（20 mg/kg/d），连续11 d。ATG的肾保护作用进行了评估，通过组织学检查和多个生化assays.Results：我们的研究结果表明，ATG显着保护肾损伤，减少肾小管扩张，上皮萎缩，胶原沉积，和tubulointerstitial compartment扩张。ATG给药显著降低巨噬细胞（CD 68阳性细胞）浸润。同时，ATG下调了梗阻肾脏中促炎趋化因子单核细胞趋化蛋白-1（MCP-1）和细胞因子（包括肿瘤坏死因子-α（TNF-α）、白细胞介素-1 β（IL-1 β）和干扰素-γ（IFN-γ））的mRNA水平。这与核因子-κ B（NF-κ B）的活化降低有关。ATG通过增加肾脏锰超氧化物歧化酶（SOD 2）的活性来减轻UUO诱导的氧化应激，从而降低脂质过氧化水平。此外，ATG通过降低转化生长因子-β 1（TGF-β 1）及其I型受体的丰度，抑制Smad 2/3磷酸化和核转位，上调Smad 7表达，抑制肾小管上皮-间质转化（EMT）。值得注意的是，在肾保护的功效是相当的，甚至上级losartan.Conclusion：ATG可以保护肾脏免受UUO诱导的损伤和纤维化，通过抑制炎症，氧化应激和肾小管EMT，从而支持在肾纤维化治疗中的潜在作用的ATG。(C)2017 Elsevier GmbH. All rights reserved.
Background: Renal tubulointerstitial fibrosis (TIF) is commonly the final result of a variety of progressive injuries and leads to end-stage renal disease. There are few therapeutic agents currently available for retarding the development of renal TIF.Purpose: The aim of the present study is to evaluate the role of arctigenin (ATG), a lignan component derived from dried burdock (Arctium lappa L.) fruits, in protecting the kidney against injury by unilateral ureteral obstruction (UUO) in rats.Methods: Rats were subjected to UUO and then administered with vehicle, ATG (1 and 3 mg/kg/d), or losartan (20 mg/kg/d) for 11 consecutive days. The renoprotective effects of ATG were evaluated by histological examination and multiple biochemical assays.Results: Our results suggest that ATG significantly protected the kidney from injury by reducing tubular dilatation, epithelial atrophy, collagen deposition, and tubulointerstitial compartment expansion. ATG administration dramatically decreased macrophage (CD68-positive cell) infiltration. Meanwhile, ATG down-regulated the mRNA levels of pro-inflammatory chemokine monocyte chemoattractant protein-1 (MCP-1) and cytokines, including tumor necrosis factor-alpha(TNF-alpha), interleukin-1 beta(IL-1 beta), and interferon-gamma(IFN-gamma), in the obstructed kidneys. This was associated with decreased activation of nuclear factor kappa B (NF-kappa B). ATG attenuated UUO-induced oxidative stress by increasing the activity of renal manganese superoxide dismutase (SOD2), leading to reduced levels of lipid peroxidation. Furthermore, ATG inhibited the epithelial-mesenchymal transition (EMT) of renal tubules by reducing the abundance of transforming growth factor-beta 1 (TGF-beta 1) and its type I receptor, suppressing Smad2/3 phosphorylation and nuclear translocation, and up-regulating Smad7 expression. Notably, the efficacy of ATG in renal protection was comparable or even superior to losartan.Conclusion: ATG could protect the kidney from UUO-induced injury and fibrogenesis by suppressing inflammation, oxidative stress, and tubular EMT, thus supporting the potential role of ATG in renal fibrosis treatment. (C) 2017 Elsevier GmbH. All rights reserved.