Mujais S K
Department of Medicine, Northwestern University Medical School and VA Chicago Healthcare System, IL, USA.
Semin Nephrol. 1998 Jan;18(1):74-82.
By analogy to the findings with other transport disorders such as Bartter's or Liddle's syndrome, it might be expected that the various forms of renal tubular acidosis (RTA) could result from defects in H-ATPase or H-K-ATPase. However, the available data do not yet support such a simple explanation. With regard to distal RTA, inhibition of H-K-ATPase with inhibitors such as vanadate blocks the increase in enzyme activity observed with potassium depletion, but does not produce distal RTA. H-K-ATPase does not increase with metabolic acidosis, and inhibition of its activity does not decrease ammonium or total acid excretion unless K depletion is also present. Maleic acid administration produces proximal RTA along with other proximal tubular dysfunction in experimental animals. However, it acts by reducing Na,K-ATPase activity rather than by affecting specific H+ ion transporters. This is pertinent to the findings that Na,K-ATPase activity is reduced in obstructive uropathy. Although the acidification defect in this disorder has been ascribed to a defect in H-ATPase, Na-K-ATPase function is also impaired. Thus, the role of isolated defects in H+ transporters in the development of clinical acidification disorders remains to be elucidated.
与其他转运障碍（如巴特综合征或利德尔综合征）的研究结果类似，可以预期各种形式的肾小管酸中毒（RTA）可能是由H - ATP酶或H - K - ATP酶缺陷引起的。然而，现有数据尚不支持这种简单的解释。关于远端RTA，用钒酸盐等抑制剂抑制H - K - ATP酶可阻断钾缺乏时观察到的酶活性增加，但不会产生远端RTA。代谢性酸中毒时H - K - ATP酶不会增加，抑制其活性也不会减少铵或总酸排泄，除非同时存在钾缺乏。在实验动物中，给予马来酸会导致近端RTA以及其他近端肾小管功能障碍。然而，其作用机制是通过降低Na，K - ATP酶活性，而不是影响特定的H⁺离子转运体。这与梗阻性肾病中Na，K - ATP酶活性降低的研究结果相关。尽管该疾病中的酸化缺陷被归因于H - ATP酶缺陷，但Na - K - ATP酶功能也受到损害。因此，H⁺转运体单一缺陷在临床酸化障碍发生发展中的作用仍有待阐明。
