替米沙坦对心房颤动患者心房肌细胞钾通道和Cx40表达的影响

Effects of Telmisartan on Expressions of Potassium Channel and Cx40 in Atrial Myocytes of Patients with Atrial Fibrillation

关键词:  心房颤动  替米沙坦  钾通道  缝隙连接蛋白40

Key words:  atrial fibrillation  telmisartan  potassium channels  Connexin 40

摘要:

目的 探讨替米沙坦对心房颤动（atrial fibrillation，AF）患者心房肌细胞钾通道和缝隙连接蛋白40（Connexin 40，Cx40）表达的影响。方法 选取11例AF患者为研究对象，心脏手术中建立体外循环并切除患者右心耳组织。采用急性酶分离法获取单个心房肌细胞，将心房肌细胞分为4组：对照组、低剂量组（10 μmol·L^-1替米沙坦）、中剂量组（30 μmol·L^-1替米沙坦）和高剂量组（100 μmol·L^-1替米沙坦）。采用CCK-8法检测各组心房肌细胞活力；qRT-PCR检测钾通道相关基因Kir2.1、Kir3.4、Kv4.3、Kv1.5及Cx40 mRNA表达水平；Western blotting检测Kir2.1、Kir3.4、Kv4.3、Kv1.5、Cx40蛋白表达情况。结果 与对照组相比，替米沙坦不同剂量组心房肌细胞存活率、Kir3.4、Kv4.3、Kv1.5 mRNA及蛋白表达水平均显著升高（P<0.05），高剂量组显著高于中、低剂量组（P<0.05）；心房肌细胞中Kir2.1、Cx40 mRNA及蛋白表达水平均显著降低（P<0.05），且高剂量组显著低于中、低剂量组（P<0.05）。结论 替米沙坦可能通过影响钾通道相关基因表达及下调心房肌细胞Cx40表达进而拮抗AF患者心房重构。

Abstract:

OBJECTIVE To investigate the effects of telmisartan on the expression of potassium channel and Connexin 40(Cx40) in atrial myocytes of patients with atrial fibrillation(AF). METHODS Eleven patients with AF were selected as the study subjects, cardiopulmonary bypass was established during cardiac surgery and the right atrial appendage tissues were excised. Acute enzymatic isolation was used to obtain single atrial myocytes, atrial myocytes were divided into four groups:control group(untreated), low dose group(10 μmol·L^-1 telmisartan), medium dose group(30 μmol·L^-1 telmisartan), and high dose group(100 μmol·L^-1 telmisartan). CCK-8 method was used to detect the viability of atrial myocytes in each group; qRT-PCR was used to detect the expressions of potassium channels related genes Kir2.1, Kir3.4, Kv4.3, Kv1.5, and Cx40 mRNA; the expressions of Kir2.1, Kir3.4, Kv4.3, Kv1.5 and Cx40 proteins were detected by Western blotting. RESULTS Compared with the control group, the survival rate of atrial myocytes, Kir3.4, Kv4.3, and Kv1.5 mRNAs and proteins expression levels in different doses of telmisartan were significantly increased(P<0.05), the high dose group was significantly higher than the middle and low dose groups(P<0.05); the expression levels of Kir2.1 and Cx40 mRNAs and proteins in atrial myocytes were significantly decreased(P<0.05), the high dose group was significantly lower than the middle and low dose groups(P<0.05). CONCLUSION Telmisartan may antagonize atrial remodeling in AF patients by affecting the expression of potassium channel-related genes and down-regulating the expression of Cx40 in atrial myocytes.