[1]赵伟,王永伟,韦冠山,等.PARP-1介导的自噬流受阻在大鼠心肌细胞缺血再灌注损伤中的作用[J].南方医科大学学报,2018,(08):975.
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PARP-1介导的自噬流受阻在大鼠心肌细胞缺血再灌注损伤中的作用()
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《南方医科大学学报》[ISSN:/CN:]

卷:
期数:
2018年08期
页码:
975
栏目:
出版日期:
2018-07-31

文章信息/Info

Title:
Role of poly(ADP-ribose) polymerases-1-mediated blockade of autophagy in ischemia/ reperfusion injury of rat cardiomyocytes
作者:
赵伟王永伟韦冠山徐世元
关键词:
PARP-1心肌缺血再灌注损伤自噬
Keywords:
poly(ADP-ribose) polymerases-1 myocardial ischemia-reperfusion injury autophagy
摘要:
目的探讨PARP-1介导的自噬流受阻在大鼠心肌缺血再灌注损伤(MIRI)中的作用。方法采用大鼠心肌细胞H9c2制备 缺血再灌注细胞模型。实验分为对照组、缺氧/复氧处理模型组、PARP-1抑制剂组、PARP-1抑制剂+模型组(PJ34+H/R组)。取 各组处理后的6孔板H9c2细胞提取总蛋白后Western blot分别检测PARP-1活性蛋白pADPr,凋亡相关蛋白Bax,细胞DNA损 伤标记蛋白p-γH2ax的表达,细胞自噬流相关蛋白:LC3BII/LC3I、Beclin-1、P62的表达量。通过GraphPad Prism 6 统计软件对 数据进行分析,比较各组间差异。结果与对照组比较,MIRI模型组PARP-1活性标记物pADPr表达更高表示PARP-1激活增 多,细胞凋亡损伤增加,DNA损伤(p-γH2ax)也增多(P<0.05)。LC3B II、beclin-1表达增高,同时p62表达也增高(P<0.05),表示自 噬流受阻。与模型组比较,加入PARP-1抑制剂后(H/R+PJ34组)可明显抑制心肌细胞内PARP-1活性(pADPr),细胞凋亡减少, 细胞DNA损伤也减轻(P<0.05);自噬相关蛋白LC3B II、beclin-1表达无明显变化,而p62表达降低(P<0.05),表明自噬流受阻情 况得到缓解(P<0.05)。结论PARP-1激活介导的自噬流受阻在大鼠MIRI中发挥着作用,通过抑制PARP-1活性后可明显逆转 自噬流受阻情况,减轻MIRI。
Abstract:
Objective To investigate the role of poly(ADP-ribose) polymerases-1 (PARP-1)-mediated blockade of autophagic flow in myocardial ischemia-reperfusion injury. Methods H9c2 cells, a rat cardiac myocyte line, were divided into control group, hypoxia/ reoxygenation model group (H/R group), PARP-1 inhibitor (PJ34) group, and PJ34 + H/R group. The total protein was extracted from the cells in each group to detect the expressions of pADPr, Bax, the DNA damage marker protein p- γH2ax, and autophagic flow-associated proteins LC3BII/LC3I, Beclin-1, and P62 using Western blotting. Results Compared with the control cells, the cells with H/R exhibited significantly increased expressions of pADPr, Bax and p-γH2ax (P<0.05). The expressions of LC3B II, beclin-1 and p62 were also increased significantly in the cells with H/R (P<0.05), indicating the block of the autophagic flow. The application of PARP-1 inhibitor PJ34 in the cells with H/R significantly inhibited the expressions of pADPr (P<0.05) and Bax (P<0.01), and alleviated DNA damage in the cells. PJ34 treatment did not cause significant changes in the expressions of LC3B II and beclin-1 but significantly decreased the expression of p62 (P<0.05) in the cells with H/R. Conclusion Block of autophagic flow mediated by PARP-1 activation plays a role in myocardial ischemiareperfusion injury, and inhibition of PARP-1 activity can reverse autophagic flow block to reduce the injury.

相似文献/References:

[1]刘祥,景桂霞,白娟,等.舒芬太尼预处理对大鼠心肌缺血再灌注时PI3K/Akt的影响[J].南方医科大学学报,2014,(03):335.
[2]黄艳平,杨天华,金植炎,等.线粒体通透性转换孔在内吗啡肽-1后处理减轻大鼠心肌缺血再灌注损伤中的作用[J].南方医科大学学报,2018,(05):547.

更新日期/Last Update: 1900-01-01