肾性高血压大鼠心房肌L型钙通道α_(1C)亚单位和Na^+-Ca^(2+)交换器mRNA变化的意义

mRNA changes of L type Ca^(2+) channel α_(1C) subunit and Na^+-Ca^(2+) exchanger in the atria of "2-kidney-1-clip" Goldblatt hypertensive rats

目的 利用“2肾 1夹”型Goldblatt高血压大鼠模型 ,观察在高血压形成过程中心房肌L型钙通道α1C亚单位 (CaL α1C)和Na+ Ca2 + 交换器 (NCX)mRNA的变化 ,在基因水平探讨其潜在的意义。方法 Sprague Dawley大鼠 ,高血压组用U型银夹夹住左肾动脉 ,右肾保留 ;假手术组只分离左肾动脉 ,不夹银夹。套尾法监测尾动脉血压 ,分别于手术后 2、4、6周处死动物 (各 6只 ) ,逆转录 聚合酶链反应 (RT PCR)半定量法分析CaL α1C和NCXmRNA的表达量 (以三磷酸甘油醛脱氢酶 ,即GAPDH为内参照 )。结果 在高血压形成过程中左心耳CaL α1C的mRNA水平在 2、4周时分别是假手术组的2 5、2 4倍 (P <0 0 1) ,6周时接近正常水平 ,右心耳在 6周才明显增多 (是假手术组的 2 5倍 ,P <0 0 1) ;左心耳NCX的mRNA水平在 4、6周分别是假手术组的 1 9、1 4倍 (P <0 0 1) ,而右心耳NCX的mRNA水平在 2、4、6周都明显增高 (分别是假手术组的 1 4、1 5、1 4倍 ,P <0 0 2 )。结论 肾性高血压大鼠在高血压形成过程中 ,心房肌CaL α1C、NCX的mRNA水平均表现为上调 ,左心房比右心房变化明显 ,与以往研究中左心室的变化类似 ,与心房颤动模型的差别较大 ,仍可能是发生房性心律失常的基质。

Objective Hypertension is one of the main causes of atrial fibrillation(AF).The occurrence of AF is closely related with electrical remodeling.We observed the mRNA changes of L type Ca 2+ channal α_ 1C subunit(CaL-α_ 1C ) and Na +-Ca 2+ exchanger(NCX)in the atria of renovascular hypertensive rats to compare with previous AF model.Methods Two-kidney-one-clip(2K1C)Goldblatt hypertensive Sprague-Dawley rats were killed at 2nd,4th,6th week after operation,sham-operated rats as control.Total mRNA of right auricular(RA) and left auricular(LA)was extracted respectively by use of Trizol reagent.Semiquantitative RT-PCR was used to estimate the mRNA changes of CaL-α_ 1C and NCX,and GAPDH was used as internal control.Results mRNA level of CaL-α_ 1C ,in LA increased to 2.5 and 2.4 times of sham level at 2nd and 4th week,and down to normal level at 6th week,while in RA,it increased to 2.5 times of sham level only at 6th week.mRNA level of NCX in LA increased to 1.9 and 1.4 times of sham level at 4th and 6th week,in RA,it increased to 1.4,1.5,1.4 times of sham level respectively at 2nd,4th,6th week.There was no significant difference in the mRNA level of CaL-α_ 1C and NCX between LA and RA.Conclusion The mRNA level of CaL-α_ 1C and NCX up-regulates in the atria of 2K1C hypertensive rats,and the changes in LA are more markedly than those in RA.The changes are similar with left ventricle in previous studies and different with most of the previous AF models,but may play a role in the genesis of atrial arrhythmias in hypertensive heart.