摘要
目的 研究阿匹莫德(apilimod)对稳态条件下小鼠体内造血细胞的影响。方法 6~8周龄雄性C57BL/6J小鼠随机分为溶剂对照组(vehicle)和apilimod注射组,分别腹腔注射溶剂和apilimod 0.2 mL/鼠。观测比较给药前后两组小鼠外周血象,外周血、脾脏和骨髓中造血干/祖细胞含量,血清中白细胞介素10(IL-10)等细胞因子含量的差异。造血干/祖细胞检测实验中另设动员剂普乐沙福(plerixafor,AMD3100)组和注射用水(WFI)对照组,分别注射AMD3100 5 mg/kg和注射用水0.2 mL。结果 apilimod 40 mg/kg单次腹腔注射给药后6~12 h小鼠外周血细胞数变化明显,药后24 h外周血象基本恢复至药前水平。药后9 h血小板数为药前值的78.2%,红细胞数与药前值差异不显著但低于同期溶剂对照组(P<0.05),淋巴细胞呈现下降而中性粒细胞和单核细胞数增加,药后9 h中性粒细胞数为药前值的8.7倍,显著高于溶剂对照组(P<0.05)。apilimod 10~50 mg/kg单次腹腔注射给药后9 h,小鼠外周血中性粒细胞数量增加与给药剂量呈正相关(R2=0.9556)。apilimod 40 mg/kg注射后9 h,apilimod组小鼠外周血和脾脏中单个核细胞(MNC)、非成熟造血细胞(Lin-)、造血祖细胞(LK)数量明显高于溶剂对照组(P<0.05),脾脏中造血干细胞(LSK)数量也较溶剂对照组明显增加(P<0.05);apilimod组外周血与脾脏中LK、LSK数与动员剂AMD3100组差异无统计学意义(P>0.05)。apilimod组小鼠骨髓中造血干/祖细胞比例和数量、细胞周期均与溶剂对照组差异无统计学意义(P>0.05)。apilimod给药引起小鼠血清中细胞因子含量改变,药后9 h血清中活性IL-12(IL-12p70)浓度下降甚至低于检测下限,而IL-10和肿瘤坏死因子-α(TNF-α)浓度升高为溶剂对照组的14.6和5.9倍。结论 apilimod对稳态条件下小鼠造血细胞数量具有明显的调控作用,apilimod单次腹腔注射给药显著影响小鼠外周血中成熟血细胞数量,尤其是升高中性粒细胞数量作用�
Objective To study the effect of apilimod on hematopoietic cells in mice under steady-state conditions.Methods 6-8-week-old male C57BL/6J mice were divided into the solvent control group(vehicle)and apilimod administration group,which were intraperitoneally injected with the vehicle and apilimod 0.2 mL/mouse,respectively.Before and after administration,peripheral blood cell counts,the absolute value of hematopoietic stem and progenitor cells from peripheral blood/spleen/bone marrow and the concentrations of such cytokines as IL-10 in serum were compared between the two groups.In the hematopoietic stem progenitor cell detection experiment,a plerixafor(AMD3100)group and water for injection(WFI)control group were set up,which were injected with AMD3100 at 5 mg/kg and WFI 0.2 mL/mouse,respectively.Results The peripheral blood cell count of mice changed significantly at 6-12 h after a single intraperitoneal injection of apilimod 40 mg/kg,but returned to the pre-administration level at 24 h post-treatment.At 9 h after apilimod injection,the number of platelets of mice treated with apilimod was 78.2%of the pre-administration number,and the red blood cell count did not change significantly,but was lower than that of the vehicle group(P<0.05).Additionally,the absolute value of lymphocytes decreased while that of neutrophils and monocytes increased.The absolute value of neutrophils at 9 h increased 8.7 times after treatment,and was significantly higher than that of the vehicle group(P<0.05).Apilimod 10-50 mg/kg increased neutrophils of mice in a dose-dependent manner at 9 h after a single intraperitoneal injection(R²=0.9556).Nine hours after injection of apilimod 40 mg/kg,the numbers of mononucleated cells(MNCs),immature hematopoietic cells(lin-)and lin-Sca-1-c-kit+cells(LK)in the peripheral blood and spleen of the apilimod group were significantly larger than those of the vehicle group(P<0.05).The number of lin-Sca-1+c-kit+cells(LSK)from spleens of apilimod-treated mice was significantly larger than that of vehicle treat
作者
王训
乔子肢
束慧
杨馨
李玉晴
张雪文
纪奥强
申星
邢爽
余祖胤
WANG Xun;QIAO Zizhi;SHU Hui;YANG Xin;LI Yuqing;ZHANG Xuewen;JI Aoqiang;SHEN Xing;XING Shuang;YU Zuyin(Institute of Radiation Medicine,Academy of Military Medical Sciences,Academy of Military Sciences,Beijing 100850,China;School of Life Sciences,Anhui Medical University,Hefei 230032,China;School of Pharmacy,Bengbu Medical University,Bengbu,Anhui 233030,China)
出处
《军事医学》
CAS
CSCD
2024年第3期180-186,共7页
Military Medical Sciences
基金
国家自然科学基金项目(81573088)。
关键词
阿匹莫德
中性粒细胞
造血祖细胞
造血干细胞
apilimod
neutrophil
hematopoietic progenitor cells
hematopoietic stem cells
