Fu Quanwei, Gao Qiaohui, Jiao Shengyuan, Da Fei, Guo Juan, Liu Yunen, Liu Junye
Department of Radiation Medical Protection, School of Military Preventive Medicine, Air Force Medical University, Xi'an 710038, China.
Shenyang Medical College, No. 146, Huanghe North Street, Shenyang 110034, China.
Regen Ther. 2024 Apr 22;27:398-407. doi: 10.1016/j.reth.2024.04.001. eCollection 2024 Dec.
Ionizing radiation-induced lung injury is caused by the initial inflammatory reaction and leads to advanced fibrosis of lung tissue. Adipose-derived stem cells (ASCs) are a type of mesenchymal stem cell that can differentiate into various functional cell types with broad application prospects in the treatment of tissue damage. The purpose of this study was to explore the protective effect of ASCs against radiation-induced lung injury and to provide a novel basis for prevention and treatment of radiation-induced lung injury.
Fifty mice were randomly divided into a control group (Ctrl), radiation exposure group (IR), radiation exposure plus ASC treatment group (IR + ASC), radiation exposure plus L-257 group (IR + L-257), and radiation exposure plus ASC treatment and L-257 group (IR + ASC + L-257). Mice in IR, IR + ASC, and IR + ASC + L-257 groups were exposed to a single whole-body dose of 5 Gy X-rays (160 kV/25 mA, 1.25 Gy/min). Within 2 h after irradiation, mice in IR + ASC and IR + ASC + L-257 groups were injected with 5 × 10 ASCs via the tail vein. Mice in IR + L-257 and IR + ASC + L-257 groups were intraperitoneally injected with 30 mg/kg L-257 in 0.5 mL saline.
The mice in the IR group exhibited lung hemorrhage, edema, pulmonary fibrosis, and inflammatory cell infiltration, increased release of proinflammatory cytokines, elevation of oxidative stress and apoptosis, and inhibition of the dimethylarginine dimethylamino hydratase 1 (DDAH1)/ADMA/eNOS signaling pathway. ASC treatment alleviated radiation-induced oxidative stress, apoptosis, and inflammation, and restored the DDAH1/ADMA/eNOS signaling pathway. However, L-257 pretreatment offset the protective effect of ASCs against lung inflammation, oxidative stress, and apoptosis.
These data suggest that ASCs ameliorate radiation-induced lung injury, and the mechanism may be mediated through the DDAH1/ADMA/eNOS signaling pathway.
电离辐射所致肺损伤由初始炎症反应引起，并导致肺组织晚期纤维化。脂肪来源干细胞（ASCs）是一种间充质干细胞，可分化为多种功能细胞类型，在组织损伤治疗中具有广阔应用前景。本研究旨在探讨ASCs对辐射诱导肺损伤的保护作用，为辐射诱导肺损伤的防治提供新依据。
50只小鼠随机分为对照组（Ctrl）、辐射暴露组（IR）、辐射暴露加ASCs治疗组（IR + ASC）、辐射暴露加L-257组（IR + L-257）以及辐射暴露加ASCs治疗和L-257组（IR + ASC + L-257）。IR组、IR + ASC组和IR + ASC + L-257组小鼠接受单次全身5 Gy X射线照射（160 kV/25 mA，1.25 Gy/min）。照射后2小时内，IR + ASC组和IR + ASC + L-257组小鼠经尾静脉注射5×10个ASCs。IR + L-257组和IR + ASC + L-257组小鼠腹腔注射溶于0.5 mL生理盐水的30 mg/kg L-257。
IR组小鼠出现肺出血、水肿、肺纤维化及炎症细胞浸润，促炎细胞因子释放增加，氧化应激和凋亡升高，二甲基精氨酸二甲胺水解酶1（DDAH1）/不对称二甲基精氨酸（ADMA）/内皮型一氧化氮合酶（eNOS）信号通路受抑制。ASCs治疗减轻了辐射诱导的氧化应激、凋亡和炎症，并恢复了DDAH1/ADMA/eNOS信号通路。然而，L-257预处理抵消了ASCs对肺部炎症、氧化应激和凋亡的保护作用。
这些数据表明，ASCs可改善辐射诱导的肺损伤，其机制可能通过DDAH1/ADMA/eNOS信号通路介导。
