钙敏感性受体活化促进缺血/再灌注损伤心肌细胞的凋亡及炎症反应
DOI:
作者:
作者单位:

作者简介:

通讯作者:

中图分类号:

基金项目:

江苏省高校自然科学基金资助(06kjb320006)


Activation of calcium-sensing receptors promoting cardiomyocytes apoptosis and inflammation induced by ischemia/reperfusion
Author:
Affiliation:

Fund Project:

  • 摘要
  • |
  • 图/表
  • |
  • 访问统计
  • |
  • 参考文献
  • |
  • 相似文献
  • |
  • 引证文献
  • |
  • 资源附件
  • |
  • 文章评论
    摘要:

    目的:探讨钙敏感性受体活化与心肌细胞缺血/再灌注损伤后凋亡及炎症反应的关系-方法:缺氧/复氧法处理新生大鼠心肌细胞,建立心肌缺血/再灌注(ischemia/reperfusion,I/R)模型-新生大鼠心肌细胞随机分为对照组-缺血/再灌注组-GdCl3(CaSR激动剂)组-GdCl3 + SB203058(p38MAPK特异抑制剂)组-TUNEL染色法检测心肌细胞凋亡;逆转录聚合酶链式反应(RT-PCR)测定钙敏感性受体(calcium-sensing receptor,CaSR)-肿瘤坏死因子-α(TNF-α)及白细胞介素-6(IL-6)的mRNA表达;免疫蛋白印迹法(Western blot)测定Caspase-3-Bcl-2 和丝裂原活化蛋白激酶(p38MAPK)的蛋白表达-结果:模拟I/R增强了CaSR-TNF-α-IL-6-p38MAPK的表达及心肌细胞凋亡;GdCl3进一步增强了上述作用,而对Caspase-3和Bcl-2则分别起着正向及负向调节作用;与GdCl3组相比,GdCl3 + SB203058组p38MAPK-TNF-α-IL-6的表达明显降低,而心肌细胞凋亡及CaSR的表达无明显改变-结论:CaSR激活不仅促进新生鼠心肌细胞I/R损伤后心肌细胞凋亡,且通过p38MAPK信号转导促进I/R区域的炎症反应-

    Abstract:

    Objective:To examine whether activation of calcium-sensing receptor(CaSR) is associated with apoptosis and inflammatory reaction of cardiomyocytes stimulated by ischemia/reperfusion(I/R). Methods:Primary neonatal rat ventricular cardiomyocytes were incubated in anoxia/reoxygenation method to establish a model of simulated I/R. And neonatal rat ventricular cardiomyocytes were randomly divided into control group,I/R group,GdCl3 (CaSR agonist) group and GdCl3+SB203058 (a specific inhibitor of p38MAPK) group. Cardiomyocyte apoptosis was detected by TUNEL assay. The expressions of CaSR,tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were detected by real reverse transcriptase polymerase chain reaction(RT-PCR). The expressions of Caspase-3,Bcl-2 and p38MAPK were detected by Western blot. Results:The simulated I/R enhances cardiomyocyte apoptosis and the expression of CaSR,TNF-α,IL-6 and p38MAPK. GdCl3 can further increase cardiomyocyte apoptosis and expression of above proteins,along with up-regulation of Caspase-3 and down-regulation of Bcl-2. Compared with GdCl3 group,the mRNA expression of TNF-α and IL-6 were markedly decreased with no significant changes of cardiomyocytes apoptosis and CaSR mRNA in GdCl3+SB203058 group. Conclusion:Activation of CaSR is not only associated with increased cardiomyocytes apoptosis after I/R injury via suppressing Bcl-2 and promoting Caspase-3 expression,but also induces inflammatory reaction via p38MAPK signaling pathway at I/R area.

    参考文献
    相似文献
    引证文献
引用本文

周雪媛,严 凌,朱铁兵,潘世阳,王连生,陶正贤,杨志健,曹克将.钙敏感性受体活化促进缺血/再灌注损伤心肌细胞的凋亡及炎症反应[J].南京医科大学学报(自然科学版),2012,(10):1366-1371

复制
分享
文章指标
  • 点击次数:
  • 下载次数:
  • HTML阅读次数:
  • 引用次数:
历史
  • 收稿日期:2012-03-13
  • 最后修改日期:
  • 录用日期:
  • 在线发布日期:
  • 出版日期:
通知关闭
郑重声明