Animal Model Establishment and Its Mechanism of Cytarabine-Iduced Myelosuppression.
10.19746/j.cnki.issn.1009-2137.2022.05.012
- Author:
Ya-Ling LI
1
,
2
;
Wei CHU
3
;
Jun-Jie LI
3
;
Juan-Juan DONG
3
;
Gao-Qin LI
4
;
Xiao-Jie JIN
3
;
Juan YAO
3
;
Yong-Qi LIU
5
Author Information
1. Provincial-Level Key Laboratory of Molecular Medicine of Major Diseases and Study on Prevention and Treatment of Traditional Chinese Medicine, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu Province, China,Key Laboratory of Dunhuang Medicine and Transformation Constructed by Chinese Ministry of Education and Gansu Province
2. Lanzhou 730000, Gansu Province, China,Gansu Cancer Clinical Medical Research Center of Integated Traditional Chinese and Western Medicine, Lanzhou 730000, Gansu Province, China.
3. Provincial-Level Key Laboratory of Molecular Medicine of Major Diseases and Study on Prevention and Treatment of Traditional Chinese Medicine, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu Province, China.
4. Gansu Cancer Clinical Medical Research Center of Integated Traditional Chinese and Western Medicine, Lanzhou 730000, Gansu Province, China.
5. Provincial-Level Key Laboratory of Molecular Medicine of Major Diseases and Study on Prevention and Treatment of Traditional Chinese Medicine, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu Province, China,Gansu Cancer Clinical Medical Research Center of Integated Traditional Chinese and Western Medicine, Lanzhou 730000, Gansu Province, China,E-mail：liuyongqi73@163.com.
- Publication Type:Journal Article
- Keywords:
cytarabine;
mouse model;
myelosuppression
- MeSH:
Animals;
Bone Marrow Cells;
Bone Marrow Diseases;
Cytarabine/adverse effects*;
Disease Models, Animal;
Mice;
Mice, Inbred C57BL
- From:
Journal of Experimental Hematology
2022;30(5):1376-1383
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To establish an optimized model of bone marrow suppression induced by cytarabine (Ara-C) in C57BL/6 mice and preliminarily explore the mechanism of myelosuppression based on the cycle and apoptosis of BMNC.
METHODS:C57BL/6 mice were intraperitoneally injected with Ara-C 50, 100 and 200 mg/kg for 7 days, respectively. The survival rate and body weight of C57BL/6 mice were monitored. The number of peripheral blood cells and bone marrow nucleated cells (BMNC) was detected, and the morphology of bone marrow, thymus and spleen were measured on the 7th, 14th and 21st day of the experiment. The cycle and apoptosis of BMNC were also detected by flow cytometry.
RESULTS:Ara-C 200 mg/kg caused 46.7% mortality in mice, and other doses had no significant effect on mortality. All doses of Ara-C induced bone marrow suppression in mice, as shown by a decrease in the number of peripheral blood cells (WBC, Neu, RBC, PLT) and BMNC (P<0.05), decrease in bone marrow hyperplasia, accompanied by immunosuppression and compensatory hematopoiesis of the spleen, and the above manifestations and duration were dose-dependent. Among them, the myelosuppression caused by Ara-C 50 mg/kg recovered quickly, and caused by Ara-C 200 mg/kg was too severe. The result of flow cytometry showed that Ara-C could cause S and G2/m arrest and increased apoptosis in BMNC.
CONCLUSION:Ara-C can induce myelosuppression in mice with a dose-dependent severity and duration, and the model of myelosuppression with Ara-C 100 mg/kg is more optimized. The mechanism is related to the inhibition of BMNC proliferation and the promotion of apoptosis.
