Sodium bicarbonate loading limits tubular cast formation independent of glomerular injury and proteinuria in Dahl salt-sensitive rats.
Sodium bicarbonate loading limits tubular cast formation independent of glomerular injury and proteinuria in Dahl salt-sensitive rats.
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碳酸氢钠负荷限制了达尔盐敏感大鼠的肾小管管型形成，与肾小球损伤和蛋白尿无关。
DOI：
10.1042/cs20171630
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
O'Connor,PaulM
中科院分区：
文献类型：
--
作者：
Ray,SarahC;Patel,Bansari;Irsik,DebraL;Sun,Jingping;Ocasio,Hiram;Crislip,GeneR;Jin,ChunhuaH;Chen,JianKang;Baban,Babak;Polichnowski,AaronJ;O'Connor,PaulM
碳酸氢钠（NaHCO 3）可减缓慢性肾病（CKD）患者的肾功能下降，但介导这种作用的机制仍不清楚。Dahl盐敏感（SS）大鼠在高盐饮食中出现高血压和进行性肾损伤;然而，在该模型中从未研究过碱负荷对肾损伤的影响。我们假设NaHCO 3通过管腔碱化保护Dahl盐敏感大鼠免受肾损伤的发展，管腔碱化限制了肾小管管型的形成，这是该模型中的一个突出病理特征。为了检验这一假设，我们测定了Dahl SS大鼠饮用溶剂（0.1 M NaCl）或NaHCO 3（0.1 M）溶液以及缺乏电压门控质子通道（Hv 1）的Dahl SS大鼠的血压和肾损伤反应。我们发现，口服碳酸氢钠减少肾小管NH 4+的生产，肾小管管型形成，和间质纤维化大鼠喂养高盐饮食2周。这种效应与血压、肾小球损伤或蛋白尿的变化无关，也与肾脏炎症状态的变化无关。我们发现Hv 1的无效突变也限制了Dahl SS大鼠的管型形成，与蛋白尿或肾小球损伤无关。由于Hv 1定位于TAL的管腔膜，我们的数据表明，在该模型中，该节段内的管腔流体的碱化限制了管型形成。继发于TAL节段内管腔碱化的管型形成减少可能介导在CKD患者中观察到的碱负荷的一些保护作用。
Sodium bicarbonate (NaHCO3) slows the decline in kidney function in patients with chronic kidney disease (CKD), yet the mechanisms mediating this effect remain unclear. The Dahl salt-sensitive (SS) rat develops hypertension and progressive renal injury when fed a high salt diet; however, the effect of alkali loading on kidney injury has never been investigated in this model. We hypothesized that NaHCO3protects from the development of renal injury in Dahl salt-sensitive rats via luminal alkalization which limits the formation of tubular casts, which are a prominent pathological feature in this model. To examine this hypothesis, we determined blood pressure and renal injury responses in Dahl SS rats drinking vehicle (0.1 M NaCl) or NaHCO3(0.1 M) solutions as well as in Dahl SS rats lacking the voltage-gated proton channel (Hv1). We found that oral NaHCO3reduced tubular NH4+production, tubular cast formation, and interstitial fibrosis in rats fed a high salt diet for 2 weeks. This effect was independent of changes in blood pressure, glomerular injury, or proteinuria and did not associate with changes in renal inflammatory status. We found that null mutation of Hv1 also limited cast formation in Dahl SS rats independent of proteinuria or glomerular injury. As Hv1 is localized to the luminal membrane of TAL, our data suggest that alkalization of the luminal fluid within this segment limits cast formation in this model. Reduced cast formation, secondary to luminal alkalization within TAL segments may mediate some of the protective effects of alkali loading observed in CKD patients.
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