Resveratrol delays polycystic kidney disease progression through attenuation of nuclear factor kappa B-induced inflammation
Resveratrol delays polycystic kidney disease progression through attenuation of nuclear factor kappa B-induced inflammation
复制标题
白藜芦醇通过减弱核因子 kappa B 诱导的炎症来延缓多囊肾病的进展
DOI：
10.1093/ndt/gfw058
复制
发表时间：
2016
影响因子：
6.1
通讯作者：
Mei Changlin
中科院分区：
文献类型：
--
作者：
Wu Ming;Gu Junhui;Mei Shuqin;Xu Dechao;Jing Ying;Yao Qing;Chen Meihan;Yang Ming;Chen Sixiu;Yang Bo;Qi Na;Hu Huimin;Wuthrich Rudolf P.;Mei Changlin
背景炎症在多囊肾病（PKD）的发病中起重要作用.目前的研究旨在研究抗炎化合物白藜芦醇在PKD的疗效，并探讨其潜在的作用机制。MethodsMale Han：SPRD（Cy/+）大鼠PKD治疗200 mg/kg/天白藜芦醇或车辆管饲5周。用不同浓度的白藜芦醇或核因子κB（NF-κB）抑制剂QNZ处理人常染色体显性（AD）PKD细胞、三维（3D）Madin-Darby犬肾细胞和斑马鱼。Cy/+大鼠双肾/总体重比降低15%，囊肿体积密度降低24%。白藜芦醇治疗的囊性肾的增殖指数和巨噬细胞浸润指数分别降低了40%和43%。白藜芦醇降低Cy/+大鼠肾脏中促炎因子单核细胞趋化蛋白-1（MCP-1）、肿瘤坏死因子-α（TNF-α）和补体因子B（CF B）的水平，同时降低NF-κB（p50/p65）的活性。在人ADPKD细胞和肾组织中证实了NF-κB的活化及其与促炎因子表达的相关性。白藜芦醇和QNZ可抑制ADPKD细胞MCP-1、TNF-α和CF B的表达，降低NF-κB活性。此外，NF-κB阻断使白藜芦醇治疗对炎症因子产生的抑制最小化。此外，白藜芦醇或QNZ抑制囊肿形成的3D囊肿和斑马鱼models. ConclusionsNF-κB信号通路被激活，并在多囊肾组织炎症部分负责。通过白藜芦醇靶向炎症可能是未来PKD治疗的新策略。
BackgroundInflammation plays an important role in polycystic kidney disease (PKD). The current study aimed to examine the efficacy of the anti-inflammatory compound resveratrol in PKD and to investigate its underlying mechanism of action.MethodsMale Han:SPRD (Cy/+) rats with PKD were treated with 200 mg/kg/day resveratrol or vehicle by gavage for 5 weeks. Human autosomal dominant (AD) PKD cells, three-dimensional (3D) Madin-Darby canine kidney cells and zebrafish were treated with various concentrations of resveratrol or the nuclear factor κB (NF-κB) inhibitor QNZ.ResultsResveratrol treatment reduced blood urea nitrogen levels and creatinine levels by 20 and 24%, respectively, and decreased two-kidney/total body weight ratio by 15% and cyst volume density by 24% in Cy/+ rats. The proliferation index and the macrophage infiltration index were reduced by 40 and 43%, respectively, in resveratrol-treated cystic kidneys. Resveratrol reduced the levels of the pro-inflammatory factors monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α) and complement factor B (CFB) in Cy/+ rat kidneys in parallel with the decreased activity of NF-κB (p50/p65). The activation of NF-κB and its correlation with pro-inflammatory factor expression were confirmed in human ADPKD cells and kidney tissues. Resveratrol and QNZ inhibited the expression of MCP-1, TNF-α and CFB and reduced NF-κB activity in ADPKD cells. Moreover, NF-κB blockage minimized the inhibition of inflammatory factor production by resveratrol treatment. Furthermore, resveratrol or QNZ inhibited cyst formation in the 3D cyst and zebrafish models.ConclusionsThe NF-κB signaling pathway is activated and partly responsible for inflammation in polycystic kidney tissues. Targeting inflammation through resveratrol could be a new strategy for PKD treatment in the future.