Shock wave induces chronic renal lesion through activation of the nuclear factor kappa B signaling pathway
Shock wave induces chronic renal lesion through activation of the nuclear factor kappa B signaling pathway
复制标题
冲击波通过激活核因子κB信号通路诱导慢性肾损伤
DOI：
10.1007/s00345-010-0515-9
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发表时间：
2010-10-01
影响因子：
3.4
通讯作者：
Zhang, Linlin
中科院分区：
文献类型：
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作者：
Li, Xiang;Xue, Yuquan;Zhang, Linlin
体外冲击波碎石术（ESWL）引起长期肾损伤的发病机制尚不清楚。本研究旨在探讨核因子kappa B（NF kappa B）信号通路在慢性冲击波肾损伤大鼠模型发病机制中的作用。材料与方法：成年雄性SD大鼠在X线引导下接受体外冲击波碎石术。分别于冲击波后1、3、7、35、105 d处死动物，检测肾组织学、肾功能及NF-κ B B活性的变化。还分析了NF κ B依赖性纤维化基因的表达。应用特异性NF-κ B B抑制剂吡咯烷二硫代氨基甲酸酯（PDTC）进一步研究NF-κ B B的参与。肾皮质NF κ B B明显活化。PDTC对冲击波引起的短暂性肾损害影响不大或无影响，但可减轻与NF κ B活化相关的长期肾损害。此外，冲击波暴露还上调了转化生长因子-β 1（TGF-β 1）的表达，PDTC可阻断这种上调，NF-κ B B在冲击波所致大鼠肾损害的发生发展中起重要作用。
The mechanisms responsible for the pathogenesis of long-term renal damage induced by extracorporeal shock wave lithotripsy (ESWL) are not clear. The present study was designed to investigate the role of nuclear factor kappa B (NF kappa B) signal pathway in the pathogenesis of chronic shock wave-induced renal damage in rat model. Materials and methods: Adult male Sprague-Dawley rats were exposed to ESWL under the guidance of X-rays. On days 1, 3, 7, 35, and 105 postexposures to shock wave, the animals were killed to examine the changes in renal histology and functions, and NF kappa B activity. The expression of NF kappa B-dependent fibrogenic genes was also analyzed. Pyrrolidine dithiocarbamate (PDTC), a specific NF kappa B inhibitor, was used to further investigate the involvement of NF kappa B.The applied shock wave caused a transient decline in renal function and induced chronic morphological changes such as tubular injury and interstitial fibrosis. NF kappa B was significantly activated in renal cortex. PDTC had little or no effects on the shock-wave-induced transient renal damage, but attenuated the long-term renal lesions associated with NF kappa B activation. In addition, the shock wave exposure also up-regulated the expression of transforming growth factor-beta 1 (TGF-beta 1), which was also blocked by PDTC.NF kappa B plays an important role in the progression of shock-wave- induced long-term renal damage in rat model.