雷帕霉素对60^Co辐照小鼠造血系统损伤的保护作用  

Rapamycin decreases irradiation-induced hematopoietic system damage

作　　者：王振[1] 宋琳[1] 张涵[1] 袁娜[1] 张素萍[1] 

机构地区：[1]苏州大学唐仲英血液学研究中心,215123

出　　处：《中华血液学杂志》2015年第4期321-325,共5页Chinese Journal of Hematology

基　　金：基金项目：国家自然科学基金青年项目（31201073）;江苏省自然科学基金青年项目（BK20130333）

摘　　要：目的探讨雷帕霉素对60^Co辐照小鼠造血系统损伤的保护作用。方法6～8周龄C57BL／6J小鼠分为未辐照组与辐照组，每组再分为雷帕霉素预处理组和对照组。雷帕霉素预处理组小鼠给予雷帕霉素4mg／kg，隔日腹腔注射，共5次，辐照组小鼠于末次注射后第2天接受60^Co全身照射（5Gy）。辐照后第0．5、1、2、3、5、7、40、70天取外周血检测白细胞计数（WBC）、淋巴细胞计数（LYM）、红细胞计数（RBC）、血红蛋白含量（HGB）及血小板计数（PLT），辐照后第5天观察小鼠胸骨骨髓有核细胞数量及内源性脾集落情况。结果①未辐照组：雷帕霉素预处理组WBC和LYM低于对照组（P值均〈0．01），RBC和HGB高于对照组（P值均〈0．05），PLT差异无统计学意义；两组小鼠骨髓有核细胞分布无差异。②辐照组：辐照后第0．5～7天雷帕霉素预处理组和对照组小鼠WBC、LYM均降低，两组比较差异无统计学意义，辐照后第40、70天均恢复，雷帕霉素预处理组均高于对照组（P〈0．05）；辐照后第3～7天RBC和HGB均降低，但雷帕霉素预处理组均高于单独辐照组（P〈0．05），在辐照后第40、70天两组之间差异无统计学意义；PLT变化无明显规律。辐照后第5天，对照组小鼠骨髓有核细胞显著减少，但雷帕霉素预处理组有核细胞减少程度较对照组轻；雷帕霉素预处理组小鼠内源性脾集落数多于对照组（40．00±12．86对13．20±2．31，P=0．035）。结论雷帕霉素预处理可以减轻60^Co辐照引起的小鼠外周血细胞和骨髓有核细胞的减少，促进造血系统恢复，保护脾造血单位。Objective To explore the protection function of rapamycin in hematopoietic system damage induced by irradiation. Methods Six to eight week old C57BL/6J male mice were used for experiment. Mice received 4 mg/kg rapamycin by i.p.injection every other day for 5 times. The day after the last injection, mice were exposed to a dose （5 Gy） of total body irradiation （TBI）. Peripheral blood was measured by a complete blood count at 0.5, 1, 2, 3, 5, 7, 40, 70 days after TBI. The hematoxylin-eosin staining was used to observe the pathologic changes in sternum obtained from mice at day 5 after TBI. CFU-S of spleen was measured by immerging in Tellyesniczky solution for 24 h at day 5 after TBI. Results Before TBI, WBC and LYM decreased in rapamycin-treated mice compared with control （P〈0.01）; RBC and HGB increased （P〈0.05）; there was no difference in PLT; HE staining of bone marrow from rapamcin- treated and control mice before irradiation showed no difference in marrow cellularity. After TBI, WBC and LYM decreased significantly, with no difference at 0.5 d to 7 d between rapamycin-treated and control. The counts of WBC and LYM in rapamycin-treated mice restored to normal at 40 d and 70 d. RBC and HGB decreased at irradiation group at 3 d to 7 d, but rapamycin stimulated them to a higher level, both of them tended to normal at 40 d and 70 d. HE staining of bone marrow after 5 day of 5 Gy irradiation, nucleated cells in control decreased significantly, but restored in rapamycin-treated mice. CFU-S results showed the colony number in rapamycin-treated mice was much higher than control mice after 5 Gyirradiation, with 40.00±12.86 and 13.20±2.31 （P=0.035）, respectively. Conclusion Administration of rapamycin to mice before irradiation protected the mice from hematopoietic damage induced by irradiation by maintaining the bone marrow nucleated cells, slowing down decrease and promoting the restoration of peripheral blood cells and protecting hematopoitic stern/progenitor cells in spleen.

关 键 词：雷帕霉素 小鼠 造血系统 血小板计数 

分 类 号：R965[医药卫生—药理学]