Vasopressin and Aquaporin-2 Water Channel in Impaired Water Excretion

在本研究中，我们证实了精氨酸加压素(AVP)和水通道蛋白-2(AQP2)在水排出障碍中的作用。在体外研究中，AQP2启动子分析阐明了AQP2 5‘侧翼区(-570~-560bp)存在张力反应元件(Tone)以及激活AQP2转录的cAMP反应元件(Cre)。细胞暴露在低渗溶液中会降低cAMP激活的AQP2启动子的活性。在体内研究中，糖皮质激素缺乏大鼠AQP2mRNA和蛋白的表达增加与血浆AVP的增加相一致。这一现象在糖皮质激素缺乏的老年大鼠中尤为明显。糖皮质激素替代治疗后大鼠AQP2mRNA和蛋白的表达均恢复正常。急性感染性疾病患者的血钠水平不同。低钠血症组血浆AVP升高，但循环血容量无下降。血浆IL-1β升高可中枢刺激血管紧张素转换酶释放，导致水排出障碍和低钠血症。20.9%的急性心肌梗死患者发病后72小时内出现低钠血症。低钠血症患者血浆AVP水平明显高于正常血钠血症患者。低钠血症患者近期和远期预后均较差。

In the present study we demonstrated the roles of arginine vasopressin (AVP) and aquaporin-2 (AQP2) water channel in impaired water excretion. In the in vitro study the AQP2 promoter assay clarified the presence of tonicity-response element (TonE) in the AQP2 5'-flanking region (-570～-560 bp) as well as cAMP-response element (CRE) for activating AQP2 transcription. An exposure of cells to hypotonic solution diminished the cAMP-activated AQP2 promoter activity. In the in vivo study the expression of AQP2 mRNA and protein were increased in concert with an increase in plasma AVP in the glucocorticoid-deficient rats. The phenomenon was much manifest in the elder rats with glucocorticoid deficiency. The enhanced expressions of AQP2 mRNA and protein were normalized in the rats after glucocorticoid replacement. Varying levels of serum Na were found in the patients with acute infectious diseases. The group of hyponatremia had an elevation of plasma AVP despite of no reduction in circulatory blood volume. The elevated plasma IL-1β could centrally stimulate AVP release, and produce impaired water excretion and hyponatremia. There was 20.9% of the patients with acute myocardial infarction having hyponatremia within 72 hours after the onset. Plasma AVP was significantly increased in the hyponatremic patients compared with that in the normonatremic ones. There was poor short- and long-term prognosis in the patients with hyponatremia.