盐酸甲氟喹促进DNA修复减轻辐射诱导的肺上皮细胞损伤

doi:10.12122/j.issn.1673-4254.2026.03.03

南方医科大学学报 ›› 2026, Vol. 46 ›› Issue (3): 497-504.doi: 10.12122/j.issn.1673-4254.2026.03.03

• 基础研究 • 上一篇

盐酸甲氟喹促进DNA修复减轻辐射诱导的肺上皮细胞损伤

张燕¹(), 温庆秋², 黄海波¹, 周美娟²(), 王建宇¹()

^1.广州市第十二人民医院职业环境与健康重点实验室，广东广州 510620
^2.南方医科大学公共卫生学院放射医学系//广东省热带病研究重点实验室，广东广州 510515

收稿日期:2025-10-15 出版日期:2026-03-20 发布日期:2026-03-26
通讯作者: 周美娟,王建宇 E-mail:18863301@qq.com;lkzmj@smu.edu.cn;13430230612@126.com
作者简介:张燕，主任医师，E-mail: 18863301@qq.com
基金资助:
国家自然科学基金(81903256);广州市市校（院）企联合资助专题（广州市职业环境与健康重点实验室）(2024A03J0434)

Mefloquine HCl promotes DNA repair and alleviates radiation-induced lung epithelial cell injury

Yan ZHANG¹(), Qingqiu WEN², Haibo HUANG¹, Meijuan ZHOU²(), Jianyu WANG¹()

^1.Key Laboratory of Occupational Environment and Health, Guangzhou Twelfth People's Hospital, Guangzhou 510620, China
^2.Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, China

Received:2025-10-15 Online:2026-03-20 Published:2026-03-26
Contact: Meijuan ZHOU, Jianyu WANG E-mail:18863301@qq.com;lkzmj@smu.edu.cn;13430230612@126.com
Supported by:
National Natural Science Foundation of China(81903256)

摘要/Abstract

摘要：

目的探讨盐酸甲氟喹（MQ）对X射线照射所致肺上皮细胞DNA损伤的保护作用。方法实验将人正常肺上皮细胞（BEAS-2B）分为空白对照组、空白对照+MQ组、单纯照射组、照射+MQ处理组；利用CCK-8实验、EdU-488实验、细胞克隆形成实验观察MQ对X射线照射后细胞增殖和放射敏感性的影响；通过流式细胞术检测不同条件处理BEAS-2B细胞的凋亡及细胞周期情况；通过细胞免疫荧光实验、彗星电泳观察MQ对BEAS-2B细胞DNA双链断裂（DSB）损伤修复的调控功能；利用Western blotting、qPCR和荧光素酶实验研究MQ调控DSB损伤修复的作用机制。结果 CCK-8结果显示MQ 0~40 μmol/L范围内，0~10 μmol/L对BEAS-2B细胞活力无明显抑制作用。与单纯照射组相比，10 Gy照射联合不同浓度（1~10 μmol/L）处理均能增强细胞活力，且10 μmol/L时细胞活力最高，故被选取为后续实验浓度；MQ处理能提高照射后BEAS-2B细胞增殖能力（P<0.05）和克隆形成率（P<0.05），降低辐射敏感性；同时单纯照射组细胞凋亡率为（17.43±0.51）%，而照射+MQ处理组细胞凋亡率降低至（14.03±0.45）%（t=8.621，P<0.05）；细胞周期检测发现，单纯照射导致G2/M期阻滞，MQ可缓解由4Gy照射导致的细胞G2/M期阻滞（P<0.05）；彗星实验和免疫荧光实验显示，与空白对照组相比，空白对照+MQ处理组的彗星尾矩与γH2AX foci差异无统计学意义；而照射+MQ处理组的彗星尾矩（P<0.05）和γH2AX foci形成数量（P<0.01）均较单纯照射组降低，DSB修复效率提高；Western blotting 实验与qPCR实验显示，与空白对照组相比，MQ处理BEAS-2B细胞48 h后，能够促进CtIP启动子活性（P<0.05），从而在mRNA和蛋白水平上上调CtIP的表达。结论 MQ通过上调CtIP表达，促进BEAS-2B的DSB修复能力，进而减轻辐射诱导的肺上皮细胞损伤。

关键词: 盐酸甲氟喹, 放射性肺损伤, DNA损伤, DNA双链断裂修复

Abstract:

Objective To investigate the protective effect of mefloquine HCl (MQ) against X-ray irradiation-induced DNA damage in lung epithelial cells. Methods Human lung epithelial cells (BEAS-2B) were divided into blank control group, irradiation group, and irradiation+MQ treatment group. The effects of MQ on cell proliferation and radiosensitivity after X-ray irradiation were assessed using CCK-8 assay, EdU-488 assay, and colony formation assay. Apoptosis and cell cycle distribution of BEAS-2B cells with different treatments were detected by flow cytometry. The effect of MQ in promoting DNA double-strand break (DSB) repair was observed using immunofluorescence staining and comet assay, and the molecule ar mechanism was explored using Western blotting, qPCR, and luciferase reporter assays. Results MQ at 0-10 μmol/L did not significantly affect BEAS-2B cell viability. Compared to the irradiated cells, treatment with 0-10 μmol/L MQ enhanced the cell viability, and the effect was the most conspicuous at 10 μmol/L. MQ treatment obviously promoted proliferation and increased clonogenic survival rate of irradiated BEAS-2B cells while reducing their radiosensitivity, and significantly lowered cell apoptosis rate following the irradiation. Cell cycle analysis revealed that MQ alleviated G2/M phase arrest induced by irradiation, and comet assay and immunofluorescence staining showed reduced comet tail moment and γH2AX foci formation in irradiation+MQ group. Western blotting and qPCR demonstrated that MQ treatment for 48 h significantly increased CtIP promoter activity and upregulated CtIP expressions at both the mRNA and protein levels. Conclusion MQ promotes DSB repair in BEAS-2B cells by upregulating CtIP expression and may thus alleviate radiation-induced lung epithelial cell injury.

Key words: mefloquine HCl, radiation-induced lung injury, DNA damage, DNA double-strand break repair

张燕, 温庆秋, 黄海波, 周美娟, 王建宇. 盐酸甲氟喹促进DNA修复减轻辐射诱导的肺上皮细胞损伤[J]. 南方医科大学学报, 2026, 46(3): 497-504.

Yan ZHANG, Qingqiu WEN, Haibo HUANG, Meijuan ZHOU, Jianyu WANG. Mefloquine HCl promotes DNA repair and alleviates radiation-induced lung epithelial cell injury[J]. Journal of Southern Medical University, 2026, 46(3): 497-504.

图/表 5

图1 不同浓度 MQ 对细胞活力及 HR 修复效率的影响

Fig.1 Effects of different concentrations of MQ on cell viability and HR repair efficiency. A: Cell viability curve. *P<0.05, **P<0.01 vs 0 μmol/L. B: Effect of MQ on HR repair efficiency. C: Effect of MQ on cell viability after irradiation. Data are presented as Mean±SD (n=3). *P<0.05.

图2 MQ对X射线照射后细胞增殖与克隆形成能力的影响

Fig.2 Effects of MQ on proliferation and colony formation capacity of X-ray-irradiated BEAS-2B cells. A: Cell proliferation after irradiation (Original magnification: ×50); B: BEAS-2B colony formation diagram. C, D: Statistical analysis diagrams. Data are presented as Mean±SD (n=3). *P<0.05, **P<0.01, ***P<0.001.

图3 流式检测MQ对X射线照射后细胞凋亡和细胞周期的影响

Fig.3 Flow cytometry analysis of the effects of MQ on apoptosis and cell cycle in X-ray-irradiated BEAS-2B cells. A, B: Apoptosis analysis by flow cytometry and statistical data. C. Statistical analysis of cell cycle. Data are presented as Mean±SD (n=3). *P<0.05.

图4 MQ对X射线照射后DSB的修复的影响

Fig.4 Effect of MQ on DNA double-strand break (DSB) repair following irradiation. A, B: Comet assay images and statistical analysis of irradiated BEAS-2B cells (×100). C, D: Immunofluorescence staining and quantification of γH2AX foci in BEAS-2B cells after irradiation (×50). Data are presented as Mean±SD (n=3). *P<0.05.

图5 MQ对CtIP蛋白及mRNA水平的影响

Fig.5 Effect of MQ on CtIP protein and mRNA levels. A: Protein expression of CtIP after MQ treatment. B: mRNA level of CtIP after MQ treatment. C: Effect of MQ on CtIP mRNA stability. D: Effect of MQ on CtIP promoter activity. Data are presented as Mean±SD (n=3). **P<0.01, ***P<0.001, ****P<0.0001.

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盐酸甲氟喹促进DNA修复减轻辐射诱导的肺上皮细胞损伤

Mefloquine HCl promotes DNA repair and alleviates radiation-induced lung epithelial cell injury

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