心房钠尿肽可能通过减少醛固酮诱导的内耳内淋巴液体积增加来抑制晕动病。

文献信息

中文摘要

背景： 既往研究提示醛固酮可能参与晕动病的发生，且心房钠尿肽（ANP）可能抑制晕动病。因此，本研究旨在探讨ANP对晕动病中醛固酮活性的抑制作用以及对醛固酮诱导的内耳内淋巴液体积变化的影响。方法：我们发现旋转刺激可引起血浆醛固酮水平升高，腹腔注射醛固酮可在豚鼠和小鼠中引起晕动病样反应，而ANP可抑制这些反应。结果：此外，醛固酮注射可诱导豚鼠内耳内淋巴液体积增加，而ANP可减轻这种内淋巴扩张。另外，旋转刺激和醛固酮注射后内耳组织中盐皮质激素受体（MR）表达增加，醛固酮处理后的培养前庭上皮细胞中MR表达也增加，而ANP可降低MR表达。在培养的前庭上皮细胞中，ANP减少了醛固酮诱导的MR核分布，以及ENaC和Na+-K+-ATP酶的表达和Na+-K+-ATP酶的膜分布。此外，ANP抑制了在模拟内淋巴液孵育的细胞中醛固酮诱导的细胞内K+浓度增加，以及在细胞外液孵育的细胞中细胞内Na+浓度增加。结论：综上所述，本研究结果提示，ANP可能通过降低血浆醛固酮水平，并通过下调下游靶蛋白表达和活性来抑制醛固酮诱导的内淋巴扩张，从而改变内耳上皮细胞中由此产生的离子浓度，发挥抗晕动病作用。

英文摘要

Previous studies have suggested that aldosterone is potentially involved in the development of motion sickness and that atrial natriuretic peptide (ANP) may inhibit it. Therefore, the present study was conducted to investigate the inhibitory effects of ANP on aldosterone activity in motion sickness and on aldosterone-induced changes in endolymph volume in the inner ear. We found that rotatory stimulation induced an elevation in plasma aldosterone levels, intraperitoneal aldosterone injection caused motion sickness-like responses in both guinea pigs and mice, and ANP inhibited these responses. Moreover, aldosterone injection induced an increase in inner ear endolymph volume in guinea pigs, whereas ANP alleviated this endolymph expansion. In addition, mineralocorticoid receptor (MR) expression was increased in the inner ear tissues after rotatory stimulation and aldosterone injection, and in cultured vestibular epithelial cells after aldosterone treatment, whereas ANP reduced MR expression. In cultured vestibular epithelial cells, ANP reduced the aldosterone-induced nuclear distribution of MR, as well as the expression of ENaC and Na+-K+-ATPase and the membrane distribution of Na+-K+-ATPase. Furthermore, ANP inhibited the aldosterone-induced increase in the intracellular K+ concentration in cells incubated with a simulated endolymph fluid, and the increase in intracellular Na+ concentration in cells incubated with an extracellular solution. In conclusion, the present results suggest that ANP may play an anti-motion sickness role by reducing the plasma aldosterone levels and inhibiting aldosterone-induced endolymph expansion by downregulating downstream target protein expression and activities, thereby altering the resultant ion concentrations in the inner ear epithelial cells.