Nojiri Takashi, Hosoda Hiroshi, Zenitani Masahiro, Tokudome Takeshi, Kimura Toru, Miura Koichi, Miyazato Mikiya, Okumura Meinoshin, Kangawa Kenji
Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, 5-7-1, Fujishirodai, Suita-City, Osaka, 565-8565, Japan.
Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Suita-City, Osaka, Japan.
Cancer Chemother Pharmacol. 2016 Jul;78(1):191-7. doi: 10.1007/s00280-016-3075-x. Epub 2016 Jun 10.
Granulocytopenia is the major toxicity associated with cisplatin treatment. Atrial natriuretic peptide (ANP) is a cardiac hormone used clinically for the treatment of acute heart failure in Japan. ANP exerts a wide range of protective effects on various organs, including the heart, blood vessels, lungs, and kidneys. This study's objective was to investigate the protective effects of ANP on cisplatin-induced granulocytopenia in mice.
The mice were divided into two groups: cisplatin with vehicle and cisplatin with ANP. ANP (1.5 μg/kg/min via osmotic pump, subcutaneously) or vehicle administration was started 1 day before cisplatin injection until the mice were killed. At 0, 2, 4, 8, and 14 days after cisplatin injection (16 mg/kg, intraperitoneally as a single dose), the white blood cell, red blood cell, and platelet counts were measured in the peripheral blood in both groups. The numbers of total and live cells and colony-forming unit-granulocyte-macrophage (CFU-GM) colonies in the bone marrow of the mice were also examined. In addition, at 0, 0.5, 1, and 2 days after cisplatin injection, serum granulocyte colony-stimulating factor (G-CSF) levels were measured.
ANP significantly attenuated the white blood cell count decrease in the peripheral blood 2 and 4 days after cisplatin injection. ANP also attenuated the decrease in the number of live cells and CFU-GM colonies in bone marrow 2, 4, and 8 days after cisplatin injection. ANP significantly increased serum G-CSF levels 1 day after cisplatin injection.
ANP has protective effects in cisplatin-induced granulocytopenia, with increased G-CSF production.
粒细胞减少是顺铂治疗相关的主要毒性反应。心房利钠肽（ANP）是一种心脏激素，在日本临床上用于治疗急性心力衰竭。ANP对包括心脏、血管、肺和肾脏在内的各种器官具有广泛的保护作用。本研究的目的是探讨ANP对顺铂诱导的小鼠粒细胞减少的保护作用。
将小鼠分为两组：顺铂加赋形剂组和顺铂加ANP组。在顺铂注射前1天开始通过渗透泵皮下给予ANP（1.5μg/kg/min）或赋形剂，直至小鼠处死。在顺铂注射（16mg/kg，腹腔内单次注射）后的0、2、4、8和14天，测量两组外周血中的白细胞、红细胞和血小板计数。还检查了小鼠骨髓中的总细胞数、活细胞数和集落形成单位-粒细胞-巨噬细胞（CFU-GM）集落数。此外，在顺铂注射后的0、0.5、1和2天，测量血清粒细胞集落刺激因子（G-CSF）水平。
ANP显著减轻了顺铂注射后2天和4天外周血白细胞计数的下降。ANP还减轻了顺铂注射后2天、4天和8天骨髓中活细胞数和CFU-GM集落数的下降。ANP显著提高了顺铂注射后1天的血清G-CSF水平。
ANP对顺铂诱导的粒细胞减少具有保护作用，并增加了G-CSF的产生。
