Soderberg L S, Barnett J B, Baker M L, Chang L W, Salari H, Sorenson J R
Department of Microbiology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock 72205.
Exp Hematol. 1988 Aug;16(7):577-80.
We have previously reported that copper(II)2(3,5-diisopropylsalicylate)4 (Cu-DIPS) significantly increased the survival rate of mice exposed to lethal irradiation. To examine whether Cu-DIPS affected hemopoietic activity, groups of mice were treated with Cu-DIPS or vehicle and assayed for in vitro interleukin 3 (IL-3)-dependent colony-forming units (CFU-C) and for committed progenitor granulocyte-macrophage CFU (GM-CFU). Cu-DIPS increased the number of splenic IL-3 CFU-C by five- to sixfold 7 days after treatment and splenic GM-CFU by 12-fold on day 24. These increases were accompanied by a 50% increase in spleen weight. Bone marrow IL-3 CFU-C and GM-CFU were not affected at 7 or 14 days after treatment, but were somewhat depressed at 24 days. In irradiated (8.0 Gy) mice treated with Cu-DIPS or vehicle, splenic IL-3 CFU-C and GM-CFU were undetectable 7 days after irradiation, but recovered more rapidly in Cu-DIPS-treated mice. By 24 days splenic IL-3 CFU-C in Cu-DIPS-treated mice recovered to 150% of normal (unirradiated) values and GM-CFU recovered to 270% of normal, whereas irradiated control values remained at 25% and 7%, respectively. The recovery of bone marrow hemopoiesis was slower than spleen, but 42 days after irradiation Cu-DIPS-treated mice had higher levels of bone marrow IL-3 CFU-C (eightfold) and GM-CFU (4.6-fold) than vehicle-treated mice. Cu-DIPS stimulated sixfold increases in renewable, pluripotent stem cells as measured by the in vivo assay of endogenous colony-forming units (CFU-Se).
我们之前报道过,二(3,5-二异丙基水杨酸)铜(II)4(Cu-DIPS)能显著提高受到致死剂量辐射的小鼠的存活率。为了研究Cu-DIPS是否影响造血活性,将小鼠分组,分别用Cu-DIPS或赋形剂处理,然后检测体外白介素3(IL-3)依赖性集落形成单位(CFU-C)以及定向祖细胞粒细胞-巨噬细胞集落形成单位(GM-CFU)。处理7天后,Cu-DIPS使脾脏IL-3 CFU-C数量增加了五到六倍,处理24天时,脾脏GM-CFU增加了12倍。这些增加伴随着脾脏重量增加50%。处理7天或14天后,骨髓IL-3 CFU-C和GM-CFU未受影响,但在24天时略有下降。在用Cu-DIPS或赋形剂处理的受辐照(8.0 Gy)小鼠中,辐照7天后脾脏IL-3 CFU-C和GM-CFU检测不到,但在Cu-DIPS处理的小鼠中恢复得更快。到24天时,Cu-DIPS处理的小鼠脾脏IL-3 CFU-C恢复到正常(未辐照)值的150%,GM-CFU恢复到正常的270%,而辐照对照组的值分别仍为25%和7%。骨髓造血的恢复比脾脏慢,但辐照42天后,Cu-DIPS处理的小鼠骨髓IL-3 CFU-C(八倍)和GM-CFU(4.6倍)水平高于赋形剂处理的小鼠。通过内源性集落形成单位(CFU-Se)的体内测定,Cu-DIPS使可再生多能干细胞增加了六倍。