Observation of effect on hypoxia acclimatization in repair of hematopoietic stem cells after acute radiation injury in mice

doi:10.3877/cma.j.issn.1673-9450.2023.04.004

Abstract

Abstract:

Objective

To investigate the effect of hypoxia acclimatization in repair of hematopoietic stem cells (HSCs) after acute radiation injury in mice.

Methods

According to random number table method, the male C57BL mice aged 6-7 weeks were divided into normoxic irradiation group and hypoxia acclimatization irradiation group. The animal model of acute radiation injury after hypoxia acclimatization was established by 6.0 Gy of one-time irradiation of ⁶⁰Co. Tail venous blood routine of mice before and after irradiation was continuously monitored. Detected the bone marrow hematopoietic stem cells in mice before and after hypoxia acclimatization by flow cytometry. Long bones of hypoxic acclimatized mice were taken for pathological analysis and VE-Cadherin immunofluorescence staining. HIF-1α and ANGPT1 were detected by ELISA in hypoxic acclimatized mice.

Results

Hypoxia acclimatization accelerated the recovery of peripheral blood after irradiation, the lowest numbers of RBC and PLT in hypoxia acclimatization irradiation group were higher than normoxic irradiation group [(7.0±0.6)×10¹²/L vs (5.1±0.4)×10¹²/L, t=2.483, P<0.05; (203±30)×10⁹/L vs (141±25)×10⁹/L, t=2.541, P<0.05]. The proportions and numbers of LSK cells and LT-HSC in the bone marrow of hypoxia acclimatization group were significantly higher than normoxic control group[(3.91±0.21)‰ vs (3.37±0.11) ‰, t=2.536, P=0.032; (7.18±0.84)×10⁴/L vs (6.01±0.82)×10⁴/L, t=2.641, P=0.029; (12.05±0.53)% vs (9.37±0.45) %, t=3.512, P=0.023; (0.74±0.12)× 10³/L vs (0.58±0.11) ×10³/L, t=2.667, P=0.027]. Hypoxia acclimatization caused proliferation and expansion of the bone marrow sinuses, and strengthened the expression of VE-Cadherin in endothelial sinusoidal cells. It also alleviated hematopoietic cell apoptosis and vascular niche damage. HIF-1α in LSK cells and ANGPT1 in the bone marrow cavity flushing supernatant increased significantly[(2.97±0.28)pg/cell vs (1.95±0.22)pg/cell, t=4.896, P=0.013; (12.30±3.70)pg/ml vs (6.25±2.70)pg/ml, t=6.742, P=0.001].

Conclusion

Hypoxia acclimatization attenuated the injuries and accelerated the repair of HSC induced by radiation. It may be related to the fact that hypoxia acclimatization regulate the long-term hematopoietic stem cell ratio, promote the expression of HIF-1α and ANGPT1 in HSC.

Key words: Hypoxic acclimatization, Radiation injury, HSC, HIF-1α, ANGPT1

Yong Quan, Xinze Ran, Mengjia Hu, Fang Chen, Naicheng Chen, Weinian Liao, Mo Chen, Mingqiang Shen, Shilei Chen, Song Wang, Junping Wang. Observation of effect on hypoxia acclimatization in repair of hematopoietic stem cells after acute radiation injury in mice[J]. Chinese Journal of Injury Repair and Wound Healing(Electronic Edition), 2023, 18(04): 293-298.

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Figures/Tables 6

References 24

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