Naito Yoshiro, Sawada Hisashi, Oboshi Makiko, Okuno Keisuke, Yasumura Seiki, Okuhara Yoshitaka, Eguchi Akiyo, Nishimura Koichi, Soyama Yuko, Asakura Masanori, Ishihara Masaharu, Tsujino Takeshi, Masuyama Tohru
Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, 663-8501, Japan.
Division of Coronary Heart Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
Heart Vessels. 2017 Nov;32(11):1410-1414. doi: 10.1007/s00380-017-1013-4. Epub 2017 Jul 1.
The interaction among heart failure (HF), chronic kidney disease (CKD), and anemia is called cardio-renal anemia syndrome. The mechanism of anemia in cardio-renal anemia syndrome is complex and remains completely unknown. We have previously reported that impaired intestinal iron transporters may contribute to the mechanism of anemia in HF using in vivo HF model rats. In this study, we assessed intestinal iron transporters in CKD model rats to investigate the association of intestinal iron transporters in the mechanism of cardio-renal anemia syndrome. CKD was induced by 5/6 nephrectomy in Sprague-Dawley rats. Sham-operated rats served as a control. After 24-week surgery, CKD rats exhibited normocytic normochromic anemia and normal serum erythropoietin levels despite of anemia. Serum iron levels were decreased in CKD rats compared with the controls. Of interest, intestinal expression of critical iron importers, such as duodenal cytochrome b (Dcyt-b) and divalent metal transporter 1 (DMT-1), was decreased in CKD rats compared with the controls. On the other hand, intestinal expression of ferroportin, an intestinal iron exporter, was not different in the control and CKD groups. Moreover, hepatic expression of hepcidin, a regulator of iron homeostasis, did not differ between the control and CKD groups. These results suggest that impaired intestinal expression of Dcyt-b and DMT-1 might be associated with the reduction of an iron uptake in CKD. Taken together, impaired these intestinal iron transporters may become a novel therapeutic target for cardio-renal anemia syndrome.
心力衰竭（HF）、慢性肾脏病（CKD）和贫血之间的相互作用被称为心肾贫血综合征。心肾贫血综合征中贫血的机制复杂，目前仍完全不清楚。我们之前使用体内HF模型大鼠报道过，肠道铁转运蛋白受损可能在心衰导致贫血的机制中起作用。在本研究中，我们评估了CKD模型大鼠的肠道铁转运蛋白，以研究肠道铁转运蛋白在心肾贫血综合征机制中的关联。通过对Sprague-Dawley大鼠进行5/6肾切除术诱导CKD。假手术大鼠作为对照。术后24周，CKD大鼠出现正细胞正色素性贫血，尽管贫血但血清促红细胞生成素水平正常。与对照组相比，CKD大鼠的血清铁水平降低。有趣的是，与对照组相比，CKD大鼠中关键铁转运蛋白的肠道表达，如十二指肠细胞色素b（Dcyt-b）和二价金属转运蛋白1（DMT-1）降低。另一方面，肠道铁输出蛋白铁转运蛋白的肠道表达在对照组和CKD组之间没有差异。此外，铁稳态调节因子铁调素的肝脏表达在对照组和CKD组之间也没有差异。这些结果表明，Dcyt-b和DMT-1的肠道表达受损可能与CKD中铁摄取减少有关。综上所述，这些肠道铁转运蛋白受损可能成为心肾贫血综合征的一个新的治疗靶点。
