期刊文献+

碘普罗胺对HK-2细胞凋亡及对Klotho/Wnt/β-catenin信号通路的影响 预览

Effect of Iopromide on the apoptosis and the signal pathway of Klotho/Wnt/β-catenin in HK-2 Cells
在线阅读 免费下载
分享 导出
摘要 目的造影剂肾病的发病机制迄今尚未完全阐明,文中旨在观察碘普罗胺对人肾近曲小管上皮细胞(HK-2)细胞凋亡以及Klotho/Wnt/β-catenin信号通路的影响,探讨碘普罗胺引起急性肾损伤的可能机制。方法用不同浓度的碘普罗胺(37、74、111、148 mgI/mL)处理HK-2细胞24 h,应用CCK-8法测定细胞活力,DAPI染色法观察细胞核凋亡形态,Western blot法测定凋亡相关蛋白Bax、Bcl-2、Cleaved-caspase-3蛋白以及Klotho、Wnt、磷酸化-β-catenin(p-β-catenin)及β-catenin蛋白表达水平。另外,加入不同剂量的N-乙酰半胱氨酸(NAC)(2、4、8、16、32 mmol/L)处理,检测NAC对碘普罗胺诱导的HK-2细胞Klotho/Wnt/β-catenin信号通路相关蛋白表达的影响。结果与对照组相比,不同浓度的碘普罗胺处理组HK-2细胞活力明显降低(P <0.05);而细胞凋亡率明显增高(P <0.05);Cleaved-caspase-3、Wnt、p-β-catenin及β-catenin蛋白表达明显升高(P <0.05),而Klotho蛋白表达水平明显降低(P <0.05)。除了37mgI/mL碘普罗胺组外,其余碘普罗胺处理组Bax/Bcl-2比值均较对照组增高(P <0.05)。加入NAC处理后,能逆转碘普罗胺对Klotho/Wnt/β-catenin信号通路蛋白表达的影响(P <0.05)。结论碘普罗胺可诱导HK-2细胞发生凋亡,其机制可能与其下调Klotho蛋白表达,激活Wnt/β-catenin信号通路有关。 Objective The pathogenesis of contrast-induced nephropathy has not been fully elucidated. The purpose of this study was to observe the effect of iopromide on apoptosis and Klotho/Wnt/β-catenin signaling pathway in human proximal tubular cells(HK-2). Methods HK-2 cells were treated with different concentrations of iopromide(37,74,111,148 mgI/mL)for 24 h. The expression of apoptosis-related protein,such as Bax,Bcl-2 and Cleaved-caspase-3 and the expression of Klotho,Wnt,phospho-β-catenin(p-β-catenin)and β-catenin protein were detected by Western blot. In addition,different doses of N-acetylcysteine(NAC)(2,4,8,16,32 mmol/L) were added to detect the effects of NAC on Klotho/Wnt/β-catenin signaling pathway in HK-2 cells induced by iopro-mide. Results Compared with the control group,the viability of HK-2 cells treated with different concentrations of iopromide was significantly decreased,while the apoptosis rate was significantly increased;the protein level of Cleaved-caspase-3,Wnt,p-β-catenin,β-catenin were up-regulated,however,the expression of Klotho was down-regualted. In addition,the ratio of Bax/Bcl-2 was significantly increased except for the 37mgI/ml iopromide group (P<0.05). Furthermore,the effect of iopromide on Klotho/Wnt/β-catenin signaling pathway could be reversed by adding NAC(P<0.05). Conclusion Iopromide can induce apoptosis in HK-2 cells,the underlying mechanism may be related to down-regulation of Klotho protein expression and activation of Wnt/β-catenin signaling pathway.
作者 陈燕玲 罗婷 高昕乐 许志威 凡栋 吴秀香 靳俊峰 王智 赵晓朵 庄晓东 CHEN Yanling;LUO Ting;GAO Xinyue;XU Zhiwei;FAN Dong;WU Xiuxiang;JIN Junfeng;WANG Zhi;ZHAO Xiaoduo;ZHUANG Xiaodong(Department of Pathophysiology,Zhuhai Campus of Zunyi Medical University,Zhuhai 519041,China)
出处 《实用医学杂志》 CAS 北大核心 2019年第5期729-733,共5页 The Journal of Practical Medicine
基金 国家自然科学基金(编号:81560133) 贵州省科技合作计划项目(编号:黔科合LH字[2015]7529号) 遵义医学院博士启动基金(编号:F-711)。
关键词 KLOTHO 凋亡 WNT Β-CATENIN 碘普罗胺 Klotho apoptosis Wnt β-catenin Iopromide
作者简介 通信作者:庄晓东E-mail:kangfuyanling@126.com.
  • 相关文献

参考文献4

二级参考文献37

  • 1Zager RA,Johnson AC,Hanson SY.Radiographic contrast media-induced tubular injury:evaluation of oxidant stress and plasma membrane integrity.Kidney Int,2003,64:128-139. 被引量:1
  • 2Haller C,Hizoh I.The cytotoxicity of iodinated radiocontrast agents on renal cells in vitro.Invest Radiol,2004,39:149-154. 被引量:1
  • 3Duan SB,Wu HW,Luo JA,et al.Assessment of renal function in the early stages of nephrotoxicity induced by iodinated contrast medium.Nephron,1999,83:122-125. 被引量:1
  • 4Dlamini Z,Mbita Z,Zungu M.Genealogy,expression,and molecular mechanisms in apoptosis.Pharmacol and Therapeutics,2004,101:1-15. 被引量:1
  • 5Saikumar P,Venkatachalam MA.Role of apoptosis in hypoxic/ischemic damage in the kidney.Semin Nephrol,2003,23:511. 被引量:1
  • 6Supavekin S,Zhang W,Kucherlapati R,et al.Diferential gene expression following early renal ischemia/reperfusion.Kidney Int,2003,63:1714-1724. 被引量:1
  • 7Yang CW,Faulkner GR,Wahba IM,et al.Expression of apoptosis-related genes in chronic cyclosporine A nephrotoxicity in mice.Am J Transplant,2002,2:391-399. 被引量:1
  • 8Kaushal GP.Role of caspases in renal tubular epithelial cell injury.Semin Nephrol,2003,23:425-431. 被引量:1
  • 9Tiwari MM,Brock RW,Megyesi JK,et al.Disruption of renal peritubular blood flow in lipopolysaccharide-induced renal failure:role of nitric oxide and caspases.Am J Physiol Renal Physiol,2005,289:F1324-F1332. 被引量:1
  • 10Goldenberg I,Matezky S.Nephropathy induced by contrast media:pathogenesis,risk factors and strategies.CMA J,2005,11:1461-1471. 被引量:1

共引文献18

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部 意见反馈