Application of CRX-527 in preparation of medicine for treating intestinal radiation injury
A 1.CRX-527, radiation damage technology, applied in the field of biomedicine, can solve the problems of low efficacy and high toxicity
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Embodiment 1
[0140] Example 1 Protective Effect of CRX-527 on Hematopoietic Damage Induced by Ionizing Radiation
[0141] First, we elucidated the protective effect of CRX-527 against ionizing radiation-induced hematopoietic damage. Under the lethal dose of 7.5Gy, the survival rate of mice in the irradiation group was 50%, while the survival rate of mice in the CRX-527 group was 100%, indicating that CRX-527 can significantly improve the survival rate of mice after irradiation ( Figure 1A ). At the same time, we recorded the body weight changes of the mice, and found that the body weight changes of the mice treated with CRX-527 were relatively gentle, while the body weight of the IR mice decreased significantly ( Figure 1B). In addition, we also detected related indicators of the hematopoietic system related to radiation damage. After IR, more nucleated cells remained in the bone marrow of CRX-527-treated mice, while the nucleated cells in the bone marrow of irradiated mice were almost...
Embodiment 2
[0142] Example 2 Effect of CRX-527 on Hematopoietic Stem Cell Differentiation
[0143] Characterization of hematopoietic stem and precursor cells in the bone marrow by flow cytometry ( Figure 2A ). Compared with normal mice, CRX-527 maintained a higher LSK (Lin - Sca-1 + c-Kit + ) cell number ( Figure 2C ) and ratio ( Figure 2D ), confirmed that CRX-527 promoted the proliferation of HSC. In order to distinguish the phenotype of hematopoietic stem cells, we found that after CRX-527 treatment, long-term hematopoietic stem cells (LT-HSCs, CD34 - CD135 - LSK) proportion decreased, short-term hematopoietic stem cells (ST-HSCs, CD34 + CD135 - LSK) ratio increases. At the same time, multipotent hematopoietic progenitor cells (MPPs, CD34 + CD135 + The proportion of LSK) was significantly increased, indicating that hematopoietic mobilization was activated, and cells differentiated into MPPs ( Figure 2B ). Mainly enriched in Lin - Sca-1 - c-Kit + Committed hematopoi...
Embodiment 3
[0144] Example 3 CRX-527 can stimulate macrophages to exert the radioprotective effect of intestinal epithelial cells
[0145] The differentiation of HSC to GMP is beneficial to the generation of monocytes and macrophages, and we detected macrophages by CD11b and F4 / 80-labeled flow cytometry ( Figure 3A ). The results showed that mouse macrophages (CD11b + F4 / 80 + ) ratio (CD11b + F4 / 80 + ) was higher than that of untreated mice ( Figure 3B ). During the entire observation period, the peripheral blood leukocytes of CRX-527-treated mice were significantly higher than those of irradiated mice ( Figure 3C ). In addition, we also found that after CRX-527 treatment, macrophages maintained a high level in the intestine ( Figure 3D -E). The colony formation analysis was carried out using the MODE-K-RAW264.7 co-culture system, and the results showed that there were significant differences in the co-culture system with or without RAW264.7 cells ( Figure 3F -G). Compared...
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