School of Public Health and Management, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
Department of Pharmacology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200092, China.
Oxid Med Cell Longev. 2021 Feb 4;2021:6610726. doi: 10.1155/2021/6610726. eCollection 2021.
Exposure to total body irradiation (TBI) causes dose- and tissue-specific lethality. However, there are few effective and nontoxic radiation countermeasures for the radiation injury. In the current study, mice were pretreated with a traditional antimicrobial agent, FZD, before TBI; the protective effects of FZD on radiation injury were evaluated by using parameters such as the spleen index and thymus index, immunohistochemical staining of intestinal tissue, and frequency of micronuclei in polychromatophilic erythrocytes of bone marrow. The intestinal epithelial cell line IEC-6 was used to investigate the underlying mechanisms. Our results indicated that FZD administration significantly improved the survival of lethal dose-irradiated mice, decreased the number of micronuclei, upregulated the number of leukocytes and immune organ indices, and restored intestinal integrity in mice after TBI. TUNEL and western blot showed that FZD protected intestinal tissue by downregulating radiation-induced apoptosis and autophagy. Meanwhile, FZD protected IEC-6 cells from radiation-induced cell death by inhibiting apoptosis and autophagy. To sum up, FZD protected against radiation-induced cell death both in vitro and in vivo through antiapoptosis and antiautophagy mechanisms.
全身照射(TBI)会导致剂量和组织特异性致死。然而,对于辐射损伤,目前还没有有效的、无毒的辐射对策。在本研究中,在 TBI 前用一种传统的抗菌剂 FZD 预处理小鼠,通过脾指数和胸腺指数、肠道组织免疫组化染色和骨髓多染红细胞微核频率等参数评估 FZD 对辐射损伤的保护作用。使用肠上皮细胞系 IEC-6 来研究潜在的机制。结果表明,FZD 给药显著提高了致死剂量照射小鼠的存活率,减少了微核数量,增加了白细胞数量和免疫器官指数,并在 TBI 后恢复了小鼠的肠道完整性。TUNEL 和 western blot 显示,FZD 通过下调辐射诱导的细胞凋亡和自噬来保护肠道组织。同时,FZD 通过抑制细胞凋亡和自噬来保护 IEC-6 细胞免受辐射诱导的细胞死亡。总之,FZD 通过抗细胞凋亡和抗自噬机制,在体内和体外均能防止辐射诱导的细胞死亡。