肾性高血压大鼠心肌Na^+-K^+-ATP酶和钙调神经磷酸酶mRNA表达及厄贝沙坦的干预作用

Expression of Na^+-K^+-ATPase and calcineurin mRNA in myocardial tissue of renovascular hypertensive rats and irbesartan intervention

目的观察肾性高血压大鼠(RHR)左心室肌组织Na+-K+-ATP和钙调神经磷酸酶(CaN)mRNA的表达及其活性以及厄贝沙坦干预。方法采用两肾一夹制造肾性高血压模型,造模成功大鼠随机分为模型组和厄贝沙坦组(50 mg.kg-1.d-1),每组7只;另设假手术组大鼠7只;测量各组大鼠术前、术后血压,用药8 w后,测量大鼠左心室质量指数(LVM I),采用实时荧光定量PCR技术检测左心室肌组织(LV)Na+-K+-ATP酶α1亚单位mRNA、CaN mRNA及心钠素(ANP)mRNA表达,生化酶学方法检测心肌Na+-K+-ATP酶、CaN活性。结果与假手术组比较,RHR血压、LVM I及心肌ANP mRNA表达明显增加,心肌Na+-K+-ATP酶α1亚单位mRNA表达及其活性明显降低,CaN mRNA表达及其活性升高;与RHR模型组比较,厄贝沙坦能降低RHR血压、LVM I及心肌ANP mRNA表达,上调Na+-K+-ATP酶α1亚单位mRNA表达(P<0.05)并增加其活性,降低CaN mRNA表达(P<0.05)及CaN活性。结论 RHR左心室肥厚发生及逆转与心肌Na+-K+-ATP酶α1亚单位mRNA、CaN mRNA的表达及其活性改变有关,心肌Na+-K+-ATP酶、CaN活性改变可能与其在mRNA表达水平改变部分相关。

Objective To evaluate the expressions of Na＋-K＋-ATPase and calcineurin（CaN） mRNA and their activities in left ventricular myocardial tissue of renovascular hypertensive rats（RHR）,and the effects of intervention with Irbesartan.Methods The renovascular hypertension was induced by ＂two kidney-one clip＂ method.RHR were randomly divided into two groups： RHR model group（n=7）,Irbesartan treated group（50 mg·kg-1·d-1,n=7）,and sham operation group（n=7） as control.Blood pressure was measured at pre-operation and after operation.After eight weeks of administration,the left ventricular mass index（LVMI） was detected.Real time PCR assay was employed to determine the mRNA levels of ANP,Na＋K＋-ATPase α1 subunit and CaN in left ventricular（LV）,and the activities of Na＋-K＋-ATPase and CaN in LV were measured by biochemistry and enzymology.Results Compared with the sham operation group,the blood pressure,LVMI,CaN activity,and the levels of ANP and CaN mRNA were increased in RHR group,the Na＋-K＋-ATPaseα1 subunit mRNA level and its activity were decreased in RHR.After treatment with Irbesartan,the blood pressure,LVMI and the level of ANP mRNA were significantly decreased.Irbesartan depressed CaN mRNA level（P0.05） and its activity,while up-regulated the mRNA level of Na＋-K＋-ATPase α1 subunit（P0.05） and Na＋-K＋-ATPase activity.Conclusions The mRNA levels of Na＋-K＋-ATPaseα1 subunit and CaN and their activities may be related to the occurrence and reverse of left ventricular hypertrophy,and the change of Na＋-K＋-ATPase and CaN activities may be partially ascribed to the mRNA levels.