Asialoerythropoietin prevents contrast-induced nephropathy
Asialoerythropoietin prevents contrast-induced nephropathy
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DOI：
10.1681/asn.2007040481
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发表时间：
2008-02-01
影响因子：
13.6
通讯作者：
Kashiwagi, Atsunori
中科院分区：
文献类型：
--
作者：
Yokomaku, Yukiyo;Sugimoto, Toshiro;Kashiwagi, Atsunori
预防造影剂肾病（CIN）的策略是次优的。最近发现促红细胞生成素在多种非造血细胞中具有细胞保护作用，因此推测非造血促红细胞生成素衍生物脱唾液酸促红细胞生成素可预防CIN。通过注射放射性造影剂loversol以及抑制前列腺素和一氧化氮的合成，在大鼠中诱导肾病。诱导肾病前给予单剂量脱唾液酸促红细胞生成素可显著减轻肾功能不全和组织学肾小管损伤。对比剂诱导的肾小管细胞凋亡在体内和体外均被脱唾液酸红细胞生成素抑制，并且这种作用在体外被Janus激酶2（JAK 2）抑制剂阻断。此外，磷酸化JAK 2/信号转导和转录激活因子5（STAT 5）和热休克蛋白70增加后，注射脱唾液酸促红细胞生成素，表明脱唾液酸促红细胞生成素的作用可能是通过激活JAK 2/STAT 5途径介导的。总的来说，这些研究结果表明，脱唾液酸红细胞生成素可能有潜力作为一种新的治疗方法，以防止CIN的能力，以保持肾功能和直接保护肾组织。
Strategies to prevent contrast-induced nephropathy (CIN) are suboptimal. Erythropoietin was recently found to be cytoprotective in a variety of nonhematopoietic cells, so it was hypothesized that the nonhematopoietic erythropoietin derivative asialoerythropoietin would prevent CIN. Nephropathy was induced in rats by injection of the radiocontrast medium loversol in addition to inhibition of prostaglandin and nitric oxide synthesis. Administration of a single dose of asialoerythropoietin before the induction of nephropathy significantly attenuated the resulting renal dysfunction and histologic renal tubular injury. Contrast-induced apoptosis of renal tubular cells was inhibited by asialoerythropoietin both in vivo and in vitro, and this effect was blocked by a Janus kinase 2 (JAK2) inhibitor in vitro. Furthermore, phospho-JAK2/signal transducer and activator of transcription 5 (STAT5) and heat-shock protein 70 increased after injection of asialoerythropoietin, suggesting that the effects of asialoerythropoietin may be mediated by the activation of the JAK2/STAT5 pathway. Overall, these findings suggest that asialoerythropoietin may have potential as a new therapeutic approach to prevent CIN given its ability to preserve renal function and directly protect renal tissue.