中国药理学通报2016，Vol.32Issue(8)：1138-1143,1144,7.DOI:10.3969/j.issn.1001-1978.2016.08.021
坏死性凋亡和 p38 MAPK 通路的相互作用介导高糖引起的 H9 c2心肌细胞损伤
Interaction between necroptosis and p38MAPK pathway mediates high glucose-induced injury in H9 c2 cardiac cells
摘要
Abstract
Aim To investigate the role of the interac-tion between necroptosis ( Nec ) and p38 mitogen-acti-vated protein kinase ( MAPK) pathway in the high glu-cose (HG)-induced H9c2 cardiac cells injury.Meth-ods The cell viability was measured by cell counter kit-8 assay .The intracellular level of reactive oxygen species ( ROS ) was tested by DCFH-DA stating fol-lowed by photofluorography .Mitochondrial membrane potential ( MMP) was detected by Rhodamine 123 stai-ning followed by photofluorography . The expression levels of receptor interaction protein 3 ( RIP3, an indi-cator of Nec ) and p38 MAPK protein were tested by Western blot assay .Results The treatment of H9c2 cardiac cells with 35 mmol・ L-1 glucose ( high glu-cose, HG) for 24 h induced considerable injuries , in-cluding a decrease in cell viability , increases in ROS generation as well as MMP loss .The co-treatment of the cells with 100 μmol・ L-1 necrostatin-1(Nec-1,a specific inhibitor of Nec ) and HG for 24 h or the pre-treatment of the cells with 3 μmol・ L-1 SB 2 0 3 5 8 0 ( an inhibitor of p38MAPK) for 60 min before HG exposure attenuated the above injuries induced by HG .Moreo-ver, the treatment of the cells with HG for 1,3,6,9, 12 ,24 ,36 and 48 h significantly increased the expres-sion levels of RIP3, peaking at 24 h.The co-treatment of the cells with 100 μmol・ L-1 Nec-1 or the pre-treatment of the cells with 3 μmol・ L-1 SB203580 considerably blocked the up-regulation of RIP3 expres-sion induced by HG .On the other hand , the co-treat-ment of the cells with 100 μmol・ L-1 Nec-1 alleviated the HG-induced up-regulation of the expression of p-p38MAPK.Conclusion The interaction between Nec and p38 MAPK pathway mediates the HG-induced inju-ry in H9c2 cardiac cells.关键词
坏死性凋亡/p38丝裂原激活蛋白激酶/相互作用/高糖/心肌细胞/损伤Key words
necroptosis/p38 mitogen-activated protein kinase/interaction/high glucose/cardiomyocyte/in-jury分类
医药卫生引用本文复制引用
梁伟杰,何洁仪,陈君,余盛龙,张稳柱,宋明才,陈景福,冯鉴强,廖新学..坏死性凋亡和 p38 MAPK 通路的相互作用介导高糖引起的 H9 c2心肌细胞损伤[J].中国药理学通报,2016,32(8):1138-1143,1144,7.基金项目
国家自然科学基金资助项目（ No 81270296）；广东省财政科技项目 （）
