药物对压力超负荷性心肌肥大的干预作用研究

Study of effects of drugs on myocardial hypertrophy due to overload

目的观察高血压心肌肥厚形成过程中肿瘤坏死因子α(TNFα)、血管紧张素(Ang)和内皮素1(ET1)水平及血管紧张素转换酶抑制剂(ACEI)与β受体阻滞剂干预作用的关系。方法采用腹主动脉缩窄法复制压力超负荷性心肌肥大大鼠模型。63只大鼠随机分为假手术组(n=15)、压力负荷组(n=16)、咪哒普利组(n=16)和卡维地洛组(n=16);于术后12周分别测定各组动物的心肌肥大指数、左心室心肌Ang、TNFα和ET1及血浆Ang、血清TNFα和ET1含量。心室肌与血浆Ang和ET1含量测定采用放射免疫法,心室肌与血清TNFα含量测定采用酶联免疫吸附法。结果术后12周压力负荷组左心室心肌明显肥大,心室肌TNFα、Ang、ET1含量,血清TNFα,血浆Ang以及ET1含量均比假手术组增高(P均<0.01),咪哒普利和卡维地洛均可显著抑制心肌肥大的发展,咪哒普利可使心室肌与血清TNFα含量下降(P均<0.01);卡维地洛使心室肌与血清TNFα含量下降,但均未恢复到假手术组水平;咪哒普利干预可使心室肌与血浆Ang含量下降,与压力负荷组比较差异有显著性(P<0.01);卡维地洛干预虽可使心室肌与血浆Ang含量下降(P均<0.01),但与压力负荷组比较差异不明显(P均>0.05)。咪哒普利组干预可使心室肌与血浆ET1含量下降24.4%和15.6%;卡维地洛干预可使心室肌与血浆ET1含量下降29.3%和23.5%。结论压力负荷可增加Ang含量,引起TNFα含量升高,可能是压力超负荷心肌肥大的主要调控路径之一。

Objective To study the relation of expression change of tumor necrosis factor-α （TNF -α）, angiotensin Ⅱ（Ang Ⅱ ）, and endothelin - 1 （ET - 1）, and the effect of imidapril on myocardial hypertrophy due to overload. Methods Sixty -three rats were randomly divided into four groups： sham operation （n=15）, overload group （n=16）, imidapril group （n=16）, and Caweidiluo group （n=16）. Hypertrophic myocardium was reproduced in rats by constricting abdominal aorta. Blood samples and heart were harvested 12 weeks after aorta constriction, and myocardial hypertrophy index, the contents of Ang Ⅱ , ET - 1 in the myocardium and plasma were determined by radioimmunoassay and TNF-α in the myocardium and plasma were dertermined by enzyme linked immunoadsorbent assay. Results Left ventricle showed obvious hypertrophy 12 weeks after operation. The contents of TNF-α, Ang Ⅱ and ET - 1 in the myocardium, and the content of TNF-α in serum, Ang Ⅱ and ET - 1 in plasma were increased compared with those of controls （all P〈 0.01 ）. The treatment of imidapril and Caweidiluo could restrain the development of left ventricle hypertrophy after operation, and imidapril decreased the contents of TNF-α, Ang Ⅱ and ET - 1 in rnyocardium compared with overload group （all P 〈 0. 01）. Imidapril lowered the contents of TNF-α in serum, Ang K and ET -1 in plasma, compared with overload group （all P〈0. 01）, but not ET - 1. Caweidiluo lowered the contents of TNF -α, Ang Ⅱ and ET - 1 in myocardium, the contents of TNF-α in serum, Ang Ⅱ and ET - 1 in plasma （all P〈0. 01） compared with overload group （both P〈0. 01 ）. Conclusion The activation of rennin-angiotensin system （RAS） by over load results to an elevation of TNF -α contents in plasma and myocardium, and it is probably one of the major regulatory pathways of myocardial hypertrophy.