Myeloprotective effects of C-type natriuretic peptide on cisplatin-induced bone marrow granulocytopenia in mice.
Myeloprotective effects of C-type natriuretic peptide on cisplatin-induced bone marrow granulocytopenia in mice.
复制标题
C型利钠肽对顺铂诱导的小鼠骨髓粒细胞减少症的骨髓保护作用。
DOI：
10.1007/s00280-016-3221-5
复制
发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Kangawa K
中科院分区：
文献类型：
--
作者：
Zenitani M;Nojiri T;Kimura T;Hosoda H;Miura K;Hino J;Nakahata K;Uehara S;Miyazato M;Oue T;Okuyama H;Kangawa K
目的顺铂是一种治疗多种恶性肿瘤的有效化疗药物。与顺铂治疗相关的主要毒性是粒细胞减少症。C型利钠肽（CNP）是利钠肽家族的一员，可保护许多器官免受毒性，包括心脏、血管、肺和肾脏。本研究的目的是探讨CNP在顺铂诱导的粒细胞减少症的小鼠模型中的骨髓保护作用。方法将小鼠分为两组：顺铂与溶剂和顺铂与CNP。在顺铂注射前两天开始CNP（2.5 μg/kg/min，通过渗透泵，皮下）或溶媒给药，并持续至小鼠处死。顺铂腹腔注射（16 mg/kg）后0、2、4、8、14 d，计数骨髓总细胞数、活细胞数和粒细胞/巨噬细胞集落形成单位（CFU-GM）。此外，在0，1，2，和4天后，顺铂注射，我们测定了CXC趋化因子受体4（CXCR 4）和趋化因子CXC配体12（CXCL 12）在骨髓中的mRNA水平。4天后顺铂注射，CNP显着降低骨髓中CXCR 4 mRNA的水平，但对CXCL 12 mRNA的水平没有影响。结论CNP发挥骨髓保护作用，顺铂诱导的粒细胞减少症，降低CXCR 4的表达。
PurposeCisplatin is an effective chemotherapeutic agent used to treat a variety of malignant tumors. The major toxicity associated with cisplatin treatment is granulocytopenia. C-type natriuretic peptide (CNP), a member of the natriuretic peptide family, protects against toxicity in many organs, including the heart, blood vessels, lung, and kidney. The objective of this study was to investigate the myeloprotective effects of CNP in a mouse model of cisplatin-induced granulocytopenia.MethodsThe mice were divided into two groups: cisplatin with vehicle and cisplatin with CNP. CNP (2.5 μg/kg/min via osmotic pump, subcutaneously) or vehicle administration was started two day before cisplatin injection, and continued until the mice were killed. At 0, 2, 4, 8, and 14 days after cisplatin injection (16 mg/kg, intraperitoneally as a single dose), we counted total and living cells and granulocyte/macrophage colony-forming units (CFU-GM) in bone marrow. In addition, at 0, 1, 2, and 4 days after cisplatin injection, we measured mRNA levels of CXC chemokine receptor 4 (CXCR4) and chemokine CXC ligand 12 (CXCL12) in bone marrow.ResultsCNP significantly attenuated the reduction in bone marrow nucleated cell count and CFU-GM in bone marrow at 4 days after cisplatin injection. Four days after cisplatin injection, CNP significantly decreased the CXCR4 mRNA level in bone marrow, but had no effect on the level of CXCL12 mRNA.ConclusionsCNP exerts myeloprotective effects in cisplatin-induced granulocytopenia and decreases CXCR4 expression.