Chinese Journal of Tissue Engineering Research ›› 2025, Vol. 29 ›› Issue (31): 6681-6687.doi: 10.12307/2025.557

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Significance of interleukin-18 expression in bone marrow and peripheral blood of rats exposed to hypoxia

Li Jinjie, Xiao Jingxue, Li Nan, Song Zhen, Zhou Yanyun, Ma Jie#br#

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  1. Li Jinjie, Xiao Jingxue, Li Nan, Song Zhen, Zhou Yanyun, Ma Jie
  • Received:2024-08-05 Accepted:2024-10-08 Online:2025-11-08 Published:2025-02-24
  • Contact: Ma Jie, MD, Associate chief physician, Qinghai University Affiliated Hospital (Clinical Medicine School), Xining 810001, Qinghai Province, China
  • About author:Li Jinjie, Master candidate, Qinghai University Affiliated Hospital (Clinical Medicine School), Xining 810001, Qinghai Province, China
  • Supported by:
    Qinghai Province “Kunlun Talents•High-end Innovation and Entrepreneurship Talents” Program, No. 2020-18 (to MJ); Qinghai Provincial Science and Technology Department Natural Science Foundation Project, No. 2020-ZJ-956Q (to MJ)

Abstract: BACKGROUND: The level of peripheral erythrocytes in rats is significantly increased under hypoxia exposure, and the proliferation of nucleated erythrocytes in the bone marrow may be one of the direct causes of the increase in peripheral erythrocytes. Previous studies have focused on the effects of factors such as erythropoietin and hypoxia-inducible factor, but little research has been done on related factors such as inflammation and immunity.
OBJECTIVE: To study the expression of interleukin-18 in bone marrow nucleated erythrocytes, bone marrow supernatant and peripheral blood of rats after hypoxia exposure, and to explore the possible role of interleukin-18 in the pathogenesis of chronic mountain sickness. 
METHODS: Sixteen healthy male SD rats were randomly divided into two groups: the experimental group was kept in a hypobaric oxygen chamber at a simulated altitude of 5 000 m for 28 days, and the control group was kept in a laboratory at an altitude of 2 260 m for 28 days. The blood routine tests of the two groups of rats were performed. The proportion of CD71+ nucleated erythrocytes in the bone marrow of the two groups of rats was determined by flow cytometry. The expressions of interleukin 18 mRNA and protein in CD71+ nucleated erythrocytes in the bone marrow of the two groups of rats were determined by RT-qPCR and western blot assay. The expressions of interleukin 18 protein in the sternum of the two groups of rats were determined by immunofluorescence. The levels of interleukin 18 in the peripheral blood and bone marrow supernatant of the two groups of rats were determined by ELISA. 
RESULTS AND CONCLUSION: (1) The indexes of erythrocyte count, hemoglobin, hematocrit, and mean hemoglobin content in peripheral blood of the experimental group were higher than those of the control group (P < 0.05). (2) The proportion in bone marrow CD71+ erythroblasts was significantly higher in the experimental group than that in the control group (P < 0.05). (3) RT-qPCR results showed that the expression of interleukin 18 mRNA in CD71+ nucleated erythrocytes in the bone marrow of rats in the experimental group was significantly higher than that in the control group (P < 0.05). (4) Western blot assay results showed that the expression of interleukin 18 protein in CD71+ nucleated erythrocytes in the bone marrow of rats in the experimental group was significantly higher than that in the control group (P < 0.05). (5) The immunofluorescence results showed that the expression of interleukin 18 protein in the sternum of rats in the experimental group was significantly higher than that in the control group (P < 0.05). (6) ELISA results exhibited that the level of interleukin 18 in the serum of rats of the experimental group was higher than that in the control group (P < 0.05), but the level of interleukin 18 in the bone marrow supernatant of rats in the experimental group was lower than that in the control group (P < 0.05). The results indicate that the increased expression of interleukin 18 in bone marrow CD71+ erythroblasts and peripheral blood of rats under hypobaric hypoxia may be involved in the proliferation of erythroblasts in bone marrow.


Key words: interleukin-18, hypoxia, bone marrow, nucleated erythrocyte, hemoglobin, peripheral blood, erythrocyte, engineered cell

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