ETA受体拮抗剂对急性肺栓塞大鼠的保护作用

目的探讨ETA受体拮抗剂安贝生坦对急性肺动脉栓塞大鼠的保护作用。方法60只SD大鼠中随机取10只作为对照组；另50只随机分为两组，模型组（25只）给予0．9％氯化钠注射液灌胃，安贝生坦组（25只）给予40mg／kg的安贝生坦灌胃。30rain后，分别自两组大鼠尾静脉注射胶原＋肾上腺素，制备急性肺栓塞模型。观察急性肺栓塞大鼠的死亡率。对未猝死大鼠继续给药，1次／d，连续1周，用多导生理记录仪记录未猝死大鼠及对照组大鼠的右心室收缩压、右心指数、平均肺动脉压的变化，用RT—PCR法测定右心室肌的心钠肽（atrial natriuretic peptide，ANP）mRNA的表达，比较安贝生坦组、模型组和对照组之间的差异。结果急性肺栓塞大鼠安贝生坦组的死亡率低于模型组（P〈0．05）；未猝死大鼠继续用药1周后，安贝生坦组右心室收缩压及平均肺动脉压低于模型组（P〈0．05），但仍高于对照组（P〈0．05）；安贝生坦组大鼠的右心指数、心肌ANPmRNA的表达低于模型组（P〈0．05）。结论ETA受体拮抗剂安贝生坦可降低急性肺栓塞大鼠的死亡率，缓解继发的肺动脉高压，改善右心室功能。

Role of ETA-receptor antagonist in protecting rats against acute pulmonary embolism

Objective To study the role of ETA-receptor antagonist, ambrisentan in protecting rats against acute pulmonary embolism （APE）. Methods Sixty SD rats were randomly divided into normal control group （n=10）, model group （n=25）, ambrisentan treatment group （n=25）. Thirty minutes after the rats in model group received intragastric injection of 0.9% normal saline and those in ambrisentan treatment group received intragastdc injection of ambrisentan （40 mg/kg）, an APE model was established by injecting collagen ＋ epinephrine via the tail vein to observe the mortality of rats. The fight ventricular systolic pressure, right ventricular index and mean pulmonary artery pressure were recorded using a multichannel physiology recorder, the expression of atrial natriuretic peptide （ANP） mRNA in right ventricular muscle was detected by RT-PCR, and the difference in 3 groups was compared after the survived rats were given drugs, once a day for 1 week. Results The mortality was obviously lower in ambrisentan treatment group than in model group （P 〈 0.05）. The right ventricular systolic pressure and mean pulmonary artery pressure were significantly lower in the survived rats of ambrisentan treatment group than in those of model group 1 week after drug treatment and significantly higher than in control group （P 〈 0.05）. Ambrisentan inhibited the expression of ANP mRNA in myocardium （P 〈 0.05） and the right ventricular index was lower in Ambrisentan group than in model group （P 〈 0.05）. Conclusion Ambrisentan, an ETA-receptor antagonist, can decrease the mortality of APC rats, relieve their secondary pulmonary arterial hypertension and improve their right ventricular function.