雷帕霉素减轻辐射诱导的造血系统损伤

[Rapamycin decreases irradiation-induced hematopoietic system damage].

作者信息

Wang Zhen, Song Lin, Zhang Han, Yuan Na, Zhang Suping

机构信息

Cyrus Tang Hematology Center, Soochow University, Suzhou 215123,China.

出版信息

Zhonghua Xue Ye Xue Za Zhi. 2015 Apr;36(4):321-5. doi: 10.3760/cma.j.issn.0253-2727.2015.04.014.

DOI:10.3760/cma.j.issn.0253-2727.2015.04.014

PMID:25916296

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7342622/

Abstract

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 Gy irradiation, 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 stem/progenitor cells in spleen.

摘要

目的

探讨雷帕霉素对辐射所致造血系统损伤的保护作用。

方法

选用6至8周龄的C57BL/6J雄性小鼠进行实验。小鼠每隔一天腹腔注射4mg/kg雷帕霉素，共注射5次。最后一次注射后的第二天，小鼠接受全身照射（TBI），剂量为5Gy。在TBI后的0.5、1、2、3、5、7、40、70天通过全血细胞计数测量外周血。采用苏木精-伊红染色观察TBI后第5天小鼠胸骨的病理变化。在TBI后第5天，将脾脏浸入特列伊斯尼茨基溶液中24小时，测量脾脏的脾集落形成单位（CFU-S）。

结果

TBI前，与对照组相比，雷帕霉素处理组小鼠的白细胞（WBC）和淋巴细胞（LYM）减少（P<0.01）；红细胞（RBC）和血红蛋白（HGB）增加（P<0.05）；血小板（PLT）无差异；照射前雷帕霉素处理组和对照组小鼠骨髓的HE染色显示骨髓细胞数量无差异。TBI后，WBC和LYM显著减少，雷帕霉素处理组和对照组在0.5天至7天无差异。雷帕霉素处理组小鼠的WBC和LYM计数在40天和70天恢复正常。照射组的RBC和HGB在3天至7天减少，但雷帕霉素将它们刺激到更高水平，两者在40天和70天趋于正常。5Gy照射5天后骨髓HE染色显示，对照组有核细胞显著减少，但雷帕霉素处理组小鼠恢复。CFU-S结果显示，5Gy照射后雷帕霉素处理组小鼠的集落数远高于对照组小鼠，分别为40.00±12.86和13.20±2.31（P=0.035）。