原发性醛固酮增多症大鼠模型的建立

Establishment of a rat model of primary hyperaldosteronism

目的建立原发性醛固酮增多症大鼠模型。方法利用微量渗透泵这一给药系统，将其埋植在大鼠背部皮下建立醛固酮增多症模型。其中模型组经微量渗透泵持续释放醛固酮（1μg／h，4周）；拮抗组除给予等量醛固酮外，每日行螺内酯灌胃（每日100mg／kg）；对照组仅泵空白溶剂。尾套法检测大鼠血压，测定血钾、钠、醛固酮浓度及血浆肾素活性。4周末使用代谢笼收集大鼠24h尿，测定尿钾、尿钠含量。结果成功建立醛固酮增多症大鼠模型，模型组大鼠2周后血压明显升高，血钾下降，呈现低肾素、高醛固酮特征，24h尿钾排出量增多，与对照组和拮抗组比较差异有统计学意义（P〈0．01）。结论借助微量渗透泵这一载体，可成功建立醛固酮增多症动物模型，方法简单，成功率较高。

Objective To introduce a method for establishing a rat model of primary hyperaldosteronism. Methods An osmotic minipump as a drug delivery system was implanted subcutaneously on the back of a rat for 4 weeks. Sprague-Dawley rats were randomly divided into three groups （ n = 8 per group ） ： model group receiving aldosterone （ 1 μg/h, subcutaneously）, antagonistic group receiving spirono- lactone （ 100 mg/kg · d^-1 ,gastric gavage） plus the equal doses of aldosterone ,control group receiving vehicle （subcutaneously）. Systolic blood pressure was measured by the tail-cuff method weekly. All rats were placed in metabolism cage for collecting the 24 h urine and measuring the content of Na ^＋ ,K ^＋ 4 weeks later. When rats were killed at the end of the experiment, blood was collected by puncturing inferior vena cava. Then serum Na^＋ ,K^＋ ,aldosterone and PRA were measured. Results The hyperaldosteronism models were successfully established. In model group, the systolic blood pressure was markedly elevated 2 weeks later, serum levels of K ~ and PRA were decreased, and plasma aldosterone level and 24 h K^＋ content in urine were increased. The differences were statistically significant compared with the other two groups （ P 〈 0.01 ）. Conclusion The rat model of hyperaldosteronism can be successfully established with an osmotic minipump. The method is characteristic of simplicity, high success and no complications. It offers an effective tool for studying the primary aldosteronism.