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中国临床药理学与治疗学 ›› 2011, Vol. 16 ›› Issue (1): 13-17.

• 基础研究 • 上一篇    下一篇

阻断p38丝裂原活化蛋白激酶信号通路对高糖培养肾小球系膜NF-κB信号通路调控影响

倪连松, 金洁娜, 郑景晨, 沈飞霞   

  1. 温州医学院附属第一医院内分泌科,温州 325000,浙江
  • 收稿日期:2010-03-11 修回日期:2010-04-24 发布日期:2020-09-16
  • 作者简介:倪连松,男,副主任医师,硕士研究生导师,主要从事糖尿病肾病发病机理及治疗研究。Tel: 13758876020 E-mail: nils1014@163.com
  • 基金资助:
    温州市科技局资助项目(Y20060066)

Effects of blocking of p38 MAPK on the signal passway of NF-κB in glomerular mesangial cells incubated with high concentration of glucose

NI Lian-song, JIN Jie-na, ZHENG Jing-chen, SHEN Fei-xia   

  1. Department of Endocrinology, the First Affiliated Hospital of Wenzhou Medical College, Wenzhou 325000, Zhejiang, China
  • Received:2010-03-11 Revised:2010-04-24 Published:2020-09-16

摘要: 目的: 探讨阻断p38丝裂原活化蛋白激酶(p38 mitogen-activated protein kinases,p38 MAPK)信号通路对高糖培养肾小球系膜NF-κB信号通路调控影响。方法: 大鼠系膜细胞株分别培养在正常糖浓度(5.5 mmol/L,对照组),高糖浓度(25 mmol/L,高糖组)及25 mmol/L葡萄糖+10 μmol/L p38 MAPK特异性抑制剂SB203580(SB组)。CCK-8测定系膜细胞增殖;Phospho-ELISA法分别检测胞浆及胞核内p38 MAPK、磷酸化p38 MAPK蛋白和总NF-κB p65、活性NF-κB p65、磷酸化NF-κB p65(S276)表达。结果: 与正常对照组比较,高糖组系膜细胞出现增殖增加;胞浆及胞核内磷酸化p38 MAPK蛋白表达上调;胞核内NLS-NF-κB、Ser276-NF-κB的表达增加;SB203580干预则能逆转这一变化。结论: 阻断p38 MAPK信号通路能下调高糖培养的系膜细胞NF-κB信号通路的活化,进而抑制系膜细胞的异常增殖。

关键词: 糖尿病肾病, 肾小球系膜细胞, p38丝裂原活化蛋白激酶, 核因子-κB, SB203580

Abstract: AIM: To investigate the effects of blocking of p38 MAPK on the signal passway of NF-κB in glomerular mesangial cells incubated with high concentration of glucose.METHODS: Rat mesangial cells(MC) were incubated in media containing 5.5 mmol/L glucose(control group), 25 mmol/L high glucose(HG group), 25 mmol/L glucose +10 μmol/L SB203580(specific inhibitor of p38 MAPK)(SB group). Cell proliferation was assessed by CCK-8. Expressions of proteins of p38 MAPK and phospho- p38 MAPK in cytoplasm and nuceli were detected by phospho-ELISA method. Total NF-κB p65, activated-NF-κB p65(NLS-NF-κB), phspho-NF-κB p65(Ser276-NF-κB) in cytoplasms and nuceli were detected by Phospho-ELISA method, too.RESULTS: Compared with control group, MC in HG group showed a high growth rate, the levels of phospho-p38 MAPK in nucli and cytoplasm were increased in HG group,and the levels of NLS-NF-κB and Ser276-NF-κB in nuceli were also increased in HG group. These changes could be reversed by treatment of SB203580.CONCLUSION: Blocking of p38 MAPK could obviously down-regulate the activities of signal passway of NF-κB of MC, then inhibite the abnormal proliferation of mesangial cells.

Key words: Diabetic nephropathy, Mesangial cells, p38 mitogen-activated protein kinases, NF-κB, SB203580  ,  ,  ,  ,  

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