Dietary iron restriction prevents further deterioration of renal damage in a chronic kidney disease rat model
Dietary iron restriction prevents further deterioration of renal damage in a chronic kidney disease rat model
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DOI：
10.1097/hjh.0b013e328360381d
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发表时间：
2013-06-01
影响因子：
4.9
通讯作者：
Masuyama, Tohru
中科院分区：
文献类型：
--
作者：
Naito, Yoshiro;Fujii, Aya;Masuyama, Tohru
目的：铁积累与慢性肾脏疾病（CKD）的发病机制有关。然而，人们对单独限制铁对CKD的影响知之甚少。我们最近报道，铁限制可以防止CKD大鼠5/6肾切除模型肾脏损害的发展。在此，我们研究了铁限制对CKD大鼠模型先前存在的高血压和肾损害的治疗作用。方法：采用Sprague-Dawley大鼠5/6肾切除术诱导CKD。术后5/6只肾切除大鼠给予限铁饮食，预防方案为1天~ 16周，抢救方案为8 ~ 16周。其他CKD大鼠给予正常饮食。结果：术后16周，CKD大鼠出现高血压和肾损害。早期干预铁限制可以防止高血压和血管重塑的发展。相比之下，限制铁的晚期干预并没有显著改善CKD大鼠先前存在的高血压和血管重构。相反，限制铁的晚期干预阻止了CKD大鼠先前存在的肾损害的进一步进展。有趣的是，铁限制导致CKD大鼠尿钠增加和尿钾排泄减少。此外，铁限制显著降低CKD大鼠肾核矿皮质激素受体的表达和Rac1活性。结论：铁限制可防止原有肾损害进一步恶化。铁限制对肾损伤的有益作用似乎与抑制肾矿皮质激素受体信号传导有关。
Objective: Iron accumulation is associated with the pathogenesis of chronic kidney disease (CKD). However, little is known about the effects of isolated iron restriction against CKD. We have recently reported that iron restriction prevents the development of renal damage in the well established 5/6 nephrectomy rat model of CKD. Herein, we investigated the therapeutic effects of iron restriction on preexisting hypertension and renal damage in a rat model of CKD.Methods: CKD was induced by 5/6 nephrectomy in Sprague-Dawley rats. After surgery, 5/6 nephrectomized rats were given an iron-restricted diet from 1 day to 16 weeks for prevention protocol or from 8 to 16 weeks for rescue protocol. Other CKD rats were given a normal diet.Results: At 16 weeks after surgery, CKD rats developed hypertension and renal damage. Early intervention with iron restriction prevented the development of hypertension and vascular remodeling. By contrast, late intervention with iron restriction did not remarkably ameliorate preexisting hypertension and vascular remodeling in CKD rats. On the contrary, late intervention with iron restriction prevented further progression of preexisting renal damage in CKD rats. Interestingly, iron restriction led to increased urinary sodium and decreased urinary potassium excretions in CKD rats. Moreover, iron restriction markedly attenuated renal expression of nuclear mineralocorticoid receptor and Rac1 activity in CKD rats.Conclusion: Iron restriction prevented further deterioration of preexisting renal damage. The beneficial effects of iron restriction on renal damage seem to be associated with inhibition of renal mineralocorticoid receptor signaling.