CARK对心肌细胞肥大的影响及其作用机制探讨  

Effect of CARK ON NFκB during Cardiac Hypertrophy

作　　者：刘怡雯[1] 甄一松[1] 谌琛[1] 惠汝太 

机构地区：[1]中国医学科学院中国协和医科大学阜外心血管病医院中德室,北京100037

出　　处：《中国分子心脏病学杂志》2004年第2期89-93,共5页Molecular Cardiology of China

摘　　要：目的 :探讨心肌细胞特异表达的基因CARK在心肌细胞中的作用。方法 :构建CARK真核表达载体 ,用脂质体介导的方法将CARK基因与NFκB Luciferase报告载体或 2 6kbNppapromoter luciferase报告载体共转染入原代培养的心肌细胞中 ,检测荧光素酶活性的变化。结果 :与转染空载体组比较 ,转染CARK基因组的NFκB 荧光素酶的活性下降了 1 3% ,(p >0 0 5 ) ,2 6kbNppapromoter 荧光素酶的活性下降了 1 9% (p >0 0 5 ) ,但无显著性差异 ;当给予心肌细胞一定的刺激时 ,其荧光素酶的活性分别显著性的下降了 4 5 %和 4 4 7% (p <0 0 5 )。结论 :当心肌细胞受到AngⅡ的刺激时 ,CARK能明显抑制ANF的表达 ,并抑制NFκB的激活 。Objective To study the effect of CARK, a cardiac- specific kinase, on cardiac hypertrophy. Methods Primary neonatal cardiomyocytes were transiently transfected with 2 × NFκB-Luciferase or 2.6kb Nppa promoter-Luciferase reporter genes with or without CARK expression vectors. After transfection, the cells were treated with or without Ang 11 for 24hours. Results Compared with the group of empty vector, the DNA-binding activity of NFκB was partly inhibited, 13% lower than the control group （p 〉 0.05）and the ANF expression level 19% lower than the control group. While the cardiomyocytes were stimulated with 100nM Ang Ⅱ, the ANF expression level in the group of CARK was significantly decreased to 55.3 % of that of the control group. And the DNA-binding activity of NFκB in the group of CARK was also significantly decreased to 55 % of that of the control group, when the cardiomyocytes-were cotransfected with the positive vector MEKK and expression vector or empty vector . Conclusion CARK can attenuate cardiac hypertrophy through the inhibition of NFκB signaling directly or indirectly.

关 键 词：核因子κB心肌肥大 心房肽 

分 类 号：R541[医药卫生—心血管疾病]