AT1R 信号在心力衰竭大鼠心室肌延迟整流钾通道表达中的作用

摘要

Objective To explore the change of delayed rectifier potassium channel expression of ventricular myocytes in heart failure rats ,and the regulation effect of angiotensin II receptor I type (AT1R) signal in the change .Methods The heart failure model of Sprague Dawley (SD) rats was es-tablished by abdominal aorta banding operation .Forty SD rats were randomly divided into four groups according to the different intervention for eight weeks which were control group (sham operation ) , heart failure (HF) group (abdominal aorta banding ) ,telmisartan (Tel ,3 .57mg .kg -1 .d-1 1) group (sham operation plus Tel treatment ) ,and HF+ Tel group (abdominal aorta banding plus Tel treat-ment) .Left ventricular posterior wall thickness (LVPWd) was measured by ultrasonic cardiogram be-fore and after intervention .NT-proBNP concentration in serum was measured by enzyme-linked immu-nosorbent assay (ELISA) .The mRNAs and proteins expression of delayed rectifier potassium channel (KCNH2 ,KCNQ1) were detected by Western-Blot (WB) and real-time reverse transcriptase-poly-merase chain reaction analysis (RT-PCR) .Results Abdominal aorta banding increased the NT-proBNP concentration in rats’serum and promoted LVPWd ,which indicating ventricular remodeling and heart failure .The mRNA expression of KCNH2 and KCNQ1 were significantly increased in rats of HF group ,whereas the protein expression of KCNH2 and KCNQ1 were obviously decreased .Tel preven-ted heart failure-induced alterations in the above mentioned mRNAs and proteins expression , NT-proBNP concentration ,and LVPWd .Conclusion Tel intervention significantly is inhibited the expres-sion alterations of delay rectification potassium channel mRNAs and proteins in ventricular myocytes of heart failure rats ,it indicates that AT1R signal plays a regular role in the channel remodeling .%目的：探讨充血性心力衰竭心室肌延迟整流钾通道表达改变及血管紧张素Ⅱ受体Ⅰ型（AT1R）的调控作用。方法 SD大鼠40只随机分为4组：对照组、心衰组、替米沙坦（Tel）组及心衰＋替米沙坦组。腹主动脉结扎构建心衰模型。干预前后超声测定左房前后径及左室后壁厚度。术后8周测血清NT-proBNP含量，心室肌组织切片 HE染色，免疫印迹和实时定量RT-PCR检测延迟整流钾离子通道Kr和Ksα-亚基KCNH2、KCNQ1蛋白和mRNA表达。结果腹主动脉狭窄明显增加大鼠血浆中NT-proBNP含量，致左室后壁肥厚，HE染色心衰组心室肌细胞明显增大，证实腹主动脉狭窄致心肌肥厚、心力衰竭。心衰组 KCNH2和KCNQ1 mRNA表达上调、对应蛋白表达下调。Tel干预显著抑制心衰心室肌KCNH2和KCNQ1 mRNA和蛋白表达的上述变化。结论心力衰竭时大鼠心室肌延迟整流钾通道Kr和Ks相关基因和蛋白表达发生改变，Tel干预可抑制上述效应，提示AT1R信号参与调控心衰心室肌细胞Kr和Ks的重构。