Extracellular ATP induces albuminuria in pregnant rats
Extracellular ATP induces albuminuria in pregnant rats
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DOI：
10.1093/ndt/gfq095
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发表时间：
2010-08-01
影响因子：
6.1
通讯作者：
Bakker, Winston W.
中科院分区：
文献类型：
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作者：
Faas, Marijke M.;van der Schaaf, Gerda;Bakker, Winston W.
背景由于先兆子痫患者循环血浆ATP浓度增加，我们测试了血浆ATP增加是否能够在妊娠期间诱导蛋白尿。通过永久性颈静脉插管向妊娠（第14天）和非妊娠大鼠输注ATP（3000 μ g/kg bw）。测定白蛋白尿，并采集血液样本用于白细胞计数、血浆ATP和血浆血红素结合蛋白活性。在妊娠第20天处死大鼠，称重胎仔和胎盘，快速冷冻肾脏和胎盘组织用于免疫组织学检查。ATP输注仅在妊娠大鼠中诱导白蛋白尿，同时伴有中性粒细胞计数增加、肾小球唾液酸糖蛋白染色和CD 39表达减少、肾小球内单核细胞明显浸润和肾小球细胞内粘附分子-1（ICAM-1）表达增加。与非妊娠大鼠相比，输注生理盐水的妊娠大鼠血浆血红素结合蛋白活性增加，但在输注ATP的妊娠大鼠中受到抑制（至非妊娠水平）。在妊娠结束时（第20天），仅在输注ATP的妊娠大鼠中观察到血浆ATP水平升高。与未孕大鼠相比，妊娠大鼠肾小球AT-1受体表达降低，而妊娠动物输注ATP后AT-1受体表达升高。目前的研究表明，ATP输注诱导的促炎反应，导致肾小球蛋白尿只在怀孕的大鼠。为什么细胞外ATP仅在妊娠条件下显示这种促炎反应尚不清楚，但可能与妊娠条件下相对增强的非特异性免疫和炎症反应特征有关。
Background. As circulating plasma ATP concentrations are increased in pre-eclampsia, we tested whether increased plasma ATP is able to induce albuminuria during pregnancy.Methods. Pregnant (day 14) and non-pregnant rats were infused with ATP (3000 mu g/kg bw) via a permanent jugular vein cannula. Albuminuria was determined, and blood samples were taken for leukocyte counts, plasma ATP and plasma haemopexin activity. At Day 20 of pregnancy, rats were sacrificed, fetuses and placentas weighed and kidney and placental tissue were snap frozen for immunohistology.Results. ATP infusion induced albuminuria exclusively in pregnant rats, together with increased neutrophil counts, decreased staining for glomerular sialoglycoproteins and CD39 expression, significant intraglomerular monocyte infiltration and increased glomerular intracellular adhesion molecule-1 (ICAM-1) expression. Plasma haemopexin activity was increased in saline-infused pregnant rats as compared to non-pregnant rats but was inhibited in pregnant ATP-infused rats (to non-pregnant levels). At the end of pregnancy (Day 20), increased plasma ATP level was exclusively seen in ATP-infused pregnant rats. In pregnant rats as compared with non-pregnant rats, we found decreased expression of glomerular AT-1 receptors, which was increased after ATP infusion exclusively in pregnant animals.Conclusion. The present study shows that ATP infusion induced a pro-inflammatory response leading to glomerular albuminuria exclusively in the pregnant rat. Why extracellular ATP showed this pro-inflammatory response exclusively in the pregnant condition is unclear but is probably related with relatively enhanced non-specific immunity and inflammatory reactions characteristic for the pregnant condition.