State Key Laboratory of Toxicology and Medical Countermeasures, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, China.
Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China.
PLoS One. 2021 Jan 29;16(1):e0238209. doi: 10.1371/journal.pone.0238209. eCollection 2021.
Ilomastat, a broad-spectrum inhibitor of matrix metalloproteinases (MMPs), has drawn attentions for its function in alleviating radiation damage. However, the detailed mechanisms of Ilomastat's protection from animal model remain not fully clear. In this study, the C57BL/6 mice were pre-administrated with Ilomastat or vihicle for 2 h, and then total body of mice were exposed to 6 Gy of γ-rays. The protective effect of Ilomastat on the hematopoietic system in the irradiated mice were investigated. We found that pretreatment with Ilomastat significantly reduced the level of TGF-β1 and TNF-α, and elevated the number of bone marrow (BM) mononuclear cells in the irradiated mice. Ilomastat pretreatment also increased the fraction of BM hematopoietic progenitor cells (HPCs) and hematopoietic stem cells (HSCs) at day 30 after irradiation, and protected the spleen of mouse from irradiation. These results suggest that Ilomastat promotes the recovery of hematopoietic injury in the irradiated mice, and thus contributes to the survival of mouse after irradiation.
依罗玛司他是一种基质金属蛋白酶（MMPs）的广谱抑制剂，因其在减轻辐射损伤方面的作用而受到关注。然而，依罗玛司他对动物模型的保护作用的详细机制尚不完全清楚。在这项研究中，C57BL/6 小鼠预先用依罗玛司他或载体处理 2 小时，然后对小鼠进行全身 6Gyγ射线照射。研究了依罗玛司他对受照射小鼠造血系统的保护作用。我们发现，依罗玛司他预处理可显著降低 TGF-β1 和 TNF-α 的水平，并增加受照射小鼠骨髓（BM）单个核细胞的数量。依罗玛司他预处理还增加了照射后 30 天 BM 造血祖细胞（HPC）和造血干细胞（HSC）的比例，并保护了受照射小鼠的脾脏。这些结果表明，依罗玛司他促进了受照射小鼠造血损伤的恢复，从而有助于照射后小鼠的存活。
