替米沙坦在牵张刺激导致的心室肌细胞延迟整流钾通道改变中的作用  

Effects of telmisartan on delayed rectifier potassium channel induced by stretch in ventricular myocytes

作　　者：杨君[1] 杨龙[1] 唐倩[2] 郑亚西[1] 何炯红[1] 胥亚楠[1] 夏桂玲 田水[1] 叶芸[1] 

机构地区：[1]贵阳医学院附属贵州省人民医院心血管内科,550004 [2]贵阳医学院附属医院心血管内科

出　　处：《国际心血管病杂志》2015年第1期51-55,共5页International Journal of Cardiovascular Disease

摘　　要：目的:探讨替米沙坦在牵张刺激导致的心室肌细胞延迟整流钾离子通道改变中的作用。方法:将体外培养的乳鼠心室肌细胞分为对照组、牵张组、替米沙坦组、牵张+替米沙坦组。定量分析细胞蛋白/DNA比值及细胞培养上清中N-末端B型利钠肽原(NT-proBNP)水平以鉴定牵张有效性。实时荧光定量PCR检测延迟整流钾离子通道基因KCNH2、KCNQ1、KCNE1和KCNE2的mRNA水平;Western blot检测KCNH2和KCNQ1蛋白表达水平。结果:牵张刺激导致心室肌细胞蛋白/DNA比值增大和细胞培养上清中NT-proBNP水平升高。与对照组相比,牵张组KCNH2、KCNQ1、KCNE1和KCNE2 mRNA水平上调;替米沙坦可明显抑制牵张刺激引起的KCNH2、KCNQ1和KCNE1变化,而对KCNE2基因无显著抑制效应。与对照组相比,牵张组KCNH2和KCNQ1蛋白表达下调;与牵张组相比,牵张+替米沙坦组KCNH2和KCNQ1蛋白水平明显上调。结论:阻断血管紧张素受体可以抑制牵张刺激引起的心室肌细胞延迟整流钾通道改变。Objective： To explore the effects of telmisartan on delayed rectifier potassium ion channel stimulated by stretch in ventrieular myocytes from neonatal rats. Methods： Ventricular myocytes isolated from neonatal rats were divided into control group, stretch group, telmisartan group and stretch ＋ telmisartan group. Alterations of protein-to-DNA ratio and N-terminal pro-brain natriuretic peptide（NT-proBNP）levels in the cell culture supernatant were used to determine the effectiveness of in vitro stretch model. The mRNA expression of delayed rectifier potassium channel genes, such as KCNH2, KCNQ1, KCNE1 and KCNE2 were assayed by real-time PCR. The protein levels of KCNH2 and KCNQ1 were analyzed by Western blot. Results：Stretch significantly increased the protein-to-DNA ratio and NT-proBNP . Compared with control group, the transcription of KCNH2, KCNQ1, KCNE1 and KCNE2 mRNA were significantly increased in stretch group. Telmisartan inhibited stretch-induced alterations in KCNH2, KCNQ1 and KCNE1 mRNA expression, but had no inhibiting effect on KCNE2. However, compared with control group, the expressions of KCNH2 and KCNQ1 proteins were significantly decreased in stretch group, which could be attenuated by telmisartan markedly.Conclusion：Blockade of angiotensin receptor can attenuate changes of delayed rectifier potassium channels induced by stretch.

关 键 词：充血性心力衰竭 牵张刺激 心室重构 延迟整流钾离子通道 

分 类 号：R96[医药卫生—药理学]