醛固酮及其受体拮抗剂对大鼠主动脉平滑肌TGF-β1表达的影响

Effect of Aldosterone and its Receptor Antagonist on Expression of Transforming Growth Factor-Beta1 in Rat Aortic Vascular Smooth Muscle Cells in vivo

目的观察醛固酮及其受体拈抗剂对大鼠主动脉平滑肌转化生长因子-β1（TGF—β1）表达的影响，初步探讨原发性醛固酮增多症发生血管重构的可能机制。方法采用皮下给药的方法建立醛固酮增多症模型，其中醛固酮组经微量渗透泵持续释放醛固酮（1ug／h）；拮抗组除给予等量醛固酮外，每13行螺内酯灌胃100mg／（kg·d）；对照组仅泵空白溶剂。尾套法检测大鼠血压，4周后处死所有大鼠，测定血钾、钠、醛固酮浓度及血浆肾素活性。分别采用RT—PCR、Western印迹检测主动脉平滑肌TGF-β1基因的表达。结果①醛固酮组大鼠血压明显升高，血钾下降，血浆肾素活性降低，与对照组相比差异具统计学意义（P〈0．01）；②醛固酮组主动脉平滑肌TGF-β1基因的表达水平明显高于对照组（P〈0．01）。螺内酯可抑制醛固酮的上述作用（P〈0．01）。结论醛固酮及其受体拮抗剂螺内酯可能通过调节血管平滑肌TGF—β1的表达，从而影响血管重构的发生。

Objective To investigate the effect of aldosterone and its receptor antagonist spironolactone on transforming growth factor-betal （TGF-β1） expression in rat aortic vascular smooth muscle cells in vivo, with the aim of elucidating the underlying molecular mechanism in vascular remodeling of primary aldosteronism. Methods Sprague-Dawley rats were randomly assigned to three groups （ n = 8 in each group） , and were given vehicle, aldosterone （ 1 ug/h, subcutaneously） , or equal dose of aldosterone plus spironolactone （ 100 mg/kg/d, gastric gavage ）, respectively via a mini-osmotic pump for 4 weeks. Systolic blood pressure was measured weekly by tail-cuff method. Serum Na^＋ , K^＋ , aldosterone and plasma renin activity （PRA） were measured 4 weeks later. TGF-β1 expression in rat aortic vascular smooth muscle was detected by RT-PCR and Western blot. Restilts （1） The hyperaldosteronism model was successfully established, displaying increased plasma aldosterone level compared with controls （ P 〈 0. 01 ） In aldosterone-treated rats, systolic blood pressure was remarkably elevated, whereas serum levels of K^＋ and PRA were reduced. （2） Aldosterome infusion enhanced TGF-β1 gene expression in rat aorta compared with controls （ P 〈 0. 01 ） . All the above detrimental effects of aldosterone were inhibitable by spironolactone （ P 〈 0. 01 ） . Conclusion Aldosterone and its receptor antagonist regulate the expression of TGF-β1 gene in vascular smooth muscle ceils, thereby influencing the process of vascular remodeling in primary aldosteronlsm.