曹方潇 1蔡晓翼 2左鑫 2卢育新 2程晓晨 2张心妍 2肖凤君 2杜丽 2马山3
作者信息
- 1. 山东中医药大学药学院,山东 济南 250355||军事医学研究院,北京 100850
- 2. 军事医学研究院,北京 100850
- 3. 山东中医药大学药学院,山东 济南 250355
- 折叠
摘要
Abstract
OBJECTIVE To investigate the protective effect of mesenchymal stem cell-derived exosome(MSC-Exo)against radiation-induced cardiovascular injury and explore the underlying mecha-nisms.METHODS ① In vitro experiments:a radiation-injured human umbilical vein endothelial cells(HUVECs)model was established,and the cells were divided into a control group,an irradiation group(exposed to 40 Gy 60Co γ-rays),and an irradiation+MSC-Exo group(MSC-Exo concentration:50 mg·L-1).Cell viability was assessed by CCK-8 assay.Reactive oxygen species(ROS)levels were measured using the DCFH-DA fluorescent probe.Mito-Tracker Green staining was used to evaluate mitochondrial morphology and function.TUNEL staining was performed to detect apoptosis.The mRNA expression levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and IL-1β were deter-mined by RT-qPCR.The protein expression of cyclic GMP-AMP synthase(cGAS)was analyzed by Western blotting.② In vivo experiments:a mouse model of radiation-induced cardiovascular injury was established via local irradiation.Female C57BL/6J mice were randomly assigned to a control group,a local irradiation group,and a local irradiation+MSC-Exo group.The chest of each of these mice was exposed to a single dose of 20 Gy γ-rays,while the rest of the body was shielded with lead bricks.MSC-Exo were administered via tail vein injection 2 h after irradiation at a dose of 200 μg per mouse,and mice in the local irradiation group received an equal volume of normal saline.Thereafter,MSC-Exo were administered once every 2 days for 2 weeks,for a total of 5 injections.Cardiac function was evalu-ated via echocardiography.Serum myocardial enzyme levels were measured with an automatic biochemical analyzer,and serum myoglobin and troponin levels were measured by ELISA.Pathological changes in cardiac tissues were observed via HE staining while myocardial collagen deposition was evaluated by Masson staining.Immunohistochemistry was used to detect cardiac microvascular recon-struction and fibrosis.RESULTS ① In vitro experiments:compared to the control group,irradiation significantly suppressed the viability of HUVECs,elevated ROS levels,induced mitochondrial damage,and increased apoptosis in the irradiation group.The expression of cGAS protein and the mRNA expression levels of TNF-α,IL-6 and IL-1β were also upregulated.Treatment with MSC-Exo significantly increased cell viability from 50.3％to 80.6％,reduced ROS levels,alleviated mitochondrial damage and apoptosis,and significantly downregulated cGAS protein expression,along with a decrease in TNF-α,IL-6 and IL-1β mRNA expressions.② In vivo experiments:compared to control group,localized irradia-tion led to impaired cardiac function,elevated serum myocardial enzyme levels,and induced progressive myocardial fibrosis in mice.Compared with localized irradiation group,treatment with MSC-Exo significantly improved cardiac function,reduced myocardial injury-related serum markers,promoted cardiac microvascular reconstruction,and significantly inhibited collagen deposition and myocardial fibrosis.CONCLUSION MSC-Exo can alleviate radiation-induced cardiovascular injury by reducing oxida-tive stress,mitochondrial dysfunction,and apoptosis,thereby promoting microvascular reconstruction.关键词
放射性心血管损伤/间充质干细胞外泌体/血管内皮细胞/氧化应激/微血管重建/心肌纤维化Key words
radiation-induced cardiovascular injury/mesenchymal stem cell-derived exosome/endothelial cells/oxidative stress/microvascular reconstruction/myocardial fibrosis分类
医药卫生
