Dimethyl fumarate inhibits NLRP3/AIM2 inflammasomes to prevent spleen radiation injury ZHANG
- Author:
Liang-Liang ZHANG
1
;
Ze-Kun WU
1
;
Yue GAO
1
;
Liang-Liang ZHANG
2
;
Chang-Kun HU
2
;
Ze-Kun WU
2
;
Zi-Qiao YAN
2
;
Ze-Bin LIAO
2
;
Yue GAO
2
;
Chang-Kun HU
3
;
Zi-Qiao YAN
4
Author Information
- Publication Type:Journal Article
- Keywords: dimethyl fumarate; inflammasome; inflammatory factor; ionizing radiation; radiation injury; splenic injury
- From: Chinese Pharmacological Bulletin 2024;40(3):521-528
- CountryChina
- Language:Chinese
- Abstract: Aim To investigate the protective effect of dimethyl fumarate on spleen injury induced by gamma radiation in mice and the related mechanism. Methods C57BL/6 mice were randomly divided into the blank control group, radiation model group and DMF administration group, which were administered once at 12 h before irradiation and once at 0. 5 h, 12 h, 24 h and 48 h after irradiation. The 30-day survival rate, body weight and pathological injury of spleen were measured after a one-time total body irradiation of Co 7 rays (8 Gy). TUNEL staining was used to detect apoptosis of spleen cells. Enzyme-linked immunoassay ( ELISA) was applied to detect the contents of TNF-a, IL-1 p, IL-6, IL-18, NLRP3 and AIM2 in spleen. Western blot test and immunofluorescence staining test was employed to verify the changes of NLRP3 and AIM2 contents in spleen tissue after irradiation. Results DMF could obviously improve the survival rate of irradiated mice, improve the weight loss of irradiated mice, re-duce the pathological injury of spleen, and inhibit the apoptosis of spleen cells after irradiation. ELISA results showed that DMF could significantly inhibit the increase of spleen inflammatory cytokines TNF-a, IL-lp, IL-6, IL-18 and inflammasome components NL-RP3 and AIM2 induced by irradiation. Western blot and tissue immunofluorescence staining also confirmed that DMF could inhibit the increase of NLRP3 and AIM2 inflammasome protein levels caused by irradiation. Meanwhile, NLRP3 agonist and AIM2 agonist could antagonize the radiation protection effect of DMF on spleen cells. Conclusion DMF can ameliorate spleen injury of Co 7-ray injured mice, and its mechanism is closely related to NLRP3/AIM2 inflamma-somes, which can be used as a potential protective drug for radiation injury.
