钙离子/钙调蛋白依赖性蛋白激酶Ⅱδ参与多柔比星导致的心肌细胞毒性反应  

Calcium/Calmodutin-dependent Protein Kinase-Ⅱ δ Involved in Doxorubicin Induced Cardio-toxicity in Experimental Rats

作　　者：秦瑶[1] 赵鸿彦[1] 张文航 王冬梅[1] 

机构地区：[1]遵义医学院附属医院心内科,贵州省遵义市563003

出　　处：《中国循环杂志》2015年第10期1004-1007,共4页Chinese Circulation Journal

基　　金：贵州省2013年度遵义医学院联合基金(黔科合J字CK-898)

摘　　要：目的:探讨钙离子/钙调蛋白依赖性蛋白激酶Ⅱδ(CaMKⅡδ)在多柔比星导致的心肌细胞毒性反应中的作用。方法:用多柔比星处理大鼠心肌细胞,检测细胞增殖情况、CaMKⅡδ基因的表达情况和活性变化。利用常间回文重复序列丛集(CRISPR)技术敲除大鼠心肌细胞CaMKⅡδ基因表达,检测CaMKⅡδ基因敲除后的大鼠心肌细胞对多柔比星诱导凋亡的应答变化。检测CaMKⅡδ基因敲除大鼠心肌细胞经多柔比星处理后核因子(NF)-κB活化的变化以及miR-146a表达情况的变化。结果:多柔比星处理抑制大鼠心肌细胞增殖,CaMKⅡδ基因的表达变化不明显,但活性显著上升。利用CRISPR技术可有效敲除CaMKⅡδ基因表达。敲除CaMKⅡδ基因后的大鼠心肌细胞对多柔比星的敏感度降低。相对于正常细胞,敲除CaMKⅡδ基因后的大鼠心肌细胞在多柔比星处理时NF-κB活化程度降低,miR-146a表达上调程度降低。结论:CaMKⅡδ参与多柔比星对心肌细胞的毒性作用,这一过程涉及NF-κB以及miR-146a。Objective： To explore the role of calcium/calmodulin-dependent protein kinase-Ⅱδ （CaMK-Ⅱδ） in doxorubicin （DOX） induced cardio-toxicity in experimental rats. Methods： ① The rat＇s cardiomyocytes were treated by DOX and the cell proliferation, protein expression and activity of CaMK-Ⅱδ were examined. ② CaMK-Ⅱδ gene was knocked out by CRISPR method, the changes of DOX induced cell apoptosis and NF-κb activity and miR-146a expression were detected. Results： DOX could inhibit cardiomyocyte proliferation, the protein expression level of CaMK-Ⅱδ was similar and the activity was increased. CRISPR method may effectively knock out CaMK-Ⅱδ gene. Compared with normal cells, the cells from CaMK-Ⅱδ knocked out rats had decreased sensitivity to DOX induction, suppressed NF-κb activation and miR-146a up-regulation. Conclusion： CaMK-Ⅱδ participated in DOX induced cardio-toxicity in experimental rats and NF-κb and miR-146a were involved in this process.

关 键 词：钙离子/钙调蛋白依赖性蛋白激酶Ⅱδ 多柔比星 心肌细胞毒性 

分 类 号：R54[医药卫生—心血管疾病]