Regulation of the proximal tubular sodium/proton exchanger NHE3 in rats with puromycin aminonucleoside (PAN)-induced nephrotic syndrome
Regulation of the proximal tubular sodium/proton exchanger NHE3 in rats with puromycin aminonucleoside (PAN)-induced nephrotic syndrome
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DOI：
10.1097/01.asn.0000028839.52271.df
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发表时间：
2002-09-01
影响因子：
13.6
通讯作者：
Navar, LG
中科院分区：
文献类型：
--
作者：
Nishiyama, A;Seth, DM;Navar, LG
肾病综合征中由于肾小球渗透选择性丧失而引起的蛋白尿过多可引起肾脏水盐处理功能紊乱，并伴有水肿形成。除了与低白蛋白血症相关的水肿和流体静力学机制外，肾小管钠转运的原发性紊乱可能有助于肾病水肿的发病机制。尽管有证据表明肾病大鼠皮质集合管钠重吸收增加，但在这种情况下近端小管钠转运是否也被激活仍存在争议。在嘌呤霉素氨基糖苷（PAN）诱导的肾病综合征大鼠模型上，研究了近端小管（PT）钠重吸收的主要途径--皮质Na/H交换蛋白NHE 3的调节。PAN大鼠在3 d内出现GFR降低、严重蛋白尿和钠潴留。10天后，刷状缘囊泡的免疫印迹显示，在肾病动物的NHE 3丰度下降。然而，在相同的囊泡制剂的Na/H逆向转运蛋白的活性没有显着改变。在肾病动物中，针对NHE 3蛋白标准化的反向转运蛋白活性增加了88%（P = 0.025）。免疫组织化学与免疫印迹相同的多克隆抗体显示PT中NHE 3丰度降低。相反，单克隆抗体2B 9的免疫反应性特异性识别NHE 3的非巨蛋白相关、转运能力池。PAN处理组大鼠的血清IL-6水平高于对照组。总之，钠重吸收增加可能与NHE 3从非活性池向活性池的转变有关，从而有助于蛋白尿状态下的钠潴留。
Excessive proteinuria due to loss of glomerular perm-selectivity in nephrotic syndrome can cause disturbances in renal salt and water handling with edema formation. Apart from oncotic and hydrostatic mechanisms associated with hypoalbuminemia, primary derangements in renal tubular sodium transport may contribute to the pathogenesis of nephrotic edema. Whereas there is evidence for an increase of cortical collecting duct sodium reabsorption in nephrotic rats, it remains controversial whether proximal tubule sodium transport may also be activated in this condition. The regulation of the cortical Na/H exchanger NHE3, the main pathway for Na reabsorption in the proximal tubule (PT), was investigated in rats with puromycin aminonucleoside (PAN)induced nephrotic syndrome. PAN rats developed reduced GFR, severe proteinuria, and sodium retention within 3 d. After 10 d, immunoblots of brush border vesicles revealed a decreased abundance of NHE3 in nephrotic animals. However, the Na/H antiporter activity in the same vesicle preparations was not significantly altered. Antiporter activity normalized for NHE3 protein was increased by 88% in nephrotic animals (P = 0.025). Immunohistochemistry with the same polyclonal antibody as for immunoblots revealed a decrease of NHE3 abundance in PT. In contrast, immunoreactivity for the monoclonal antibody 2B9, which specifically recognizes the non-megalin-associated, transport-competent pool of NHE3. was higher in PAN-treated rats than in controls. In conclusion, increased sodium reabsorption might be associated with a shift of NHE3 from an inactive pool to an active pool, thus contributing to sodium retention in a state of proteinuria.