摘要
目的探究贫铀(DU)诱导甲状腺损伤的机制,并探索其防治方法。方法将大鼠甲状腺细胞FRTL-5分别用500μmol/L的贫铀溶液作用不同时间,用CCK-8法检测细胞活力。将FRTL-5细胞暴露于不同浓度的贫铀,用Annexin V-FITC/PI染色法检测细胞凋亡情况,用Western blot检测葡萄糖调节蛋白78(GRP78)的表达,用免疫荧光染色法检测转录激活因子6(ATF6)的表达。将FRTL-5细胞暴露于500μmol/L的4-苯基丁酸(4-PBA),用CCK-8法检测细胞活力。将FRTL-5细胞分为对照组、DU组和4-PBA+DU组,分别进行相应的处理后,用CCK-8法检测细胞活力。结果贫铀导致了FRTL-5细胞活力下降和细胞凋亡;贫轴诱导FRTL-5细胞GRP78和ATF6表达增加;500μmol/L的4-PBA对FRTL-5细胞的活力没有影响;4-PBA预处理缓解了贫轴诱导的细胞活力的下降。结论贫铀通过内质网应激诱导甲状腺细胞损伤,靶向内质网应激的治疗可能具有缓解贫铀导致的甲状腺损伤的作用。
Objective To explore the mechanism of depleted uranium(DU)induced thyroid damage,and the rapeutic methods for protection of thyroid from depleted uranium.Methods Fischer rat thyroid cell line-5(FRTL-5)cells were exposed to depleted uranium(500μmol/L)for different time,and the cell viability was detected by CCK-8 assay.FRTL-5 cells were exposed to different concentrations of depleted uranium,then Annexin V-FITC/PI staining was used to observe the cell apoptosis,Western blot was used to detect the expression of glucose-regulated protein 78(GRP78),and immunofluorescent staining was used to detect the expression of activating transcription factor 6(ATF6).FRTL-5 cells were exposed to 500μmol/L 4-phenylbutyric acid(4-PBA),the cell viability was detected by CCK-8 assay.FRTL-5 cells were divided into Control group,DU group and 4-PBA+DU group,and the cell viability of FRTL-5 cells was detected by CCK-8 assay after corresponding treatment.Results Depleted uranium decreased the viability of FRTL-5 cells and increased the apoptosis of FRTL-5 cells.Depleted uranium induced an increased expression of GRP78 and ATF6 in FRTL-5 cells.4-PBA(500μmol/L)had no effect on the viability of FRTL-5 cells.4-PBA alleviated the decline of cell viability caused by depleted uranium.Conclusion Depleted uranium causes the damage to thyroid cells through endoplasmic reticulum stress,and therapy targeting endoplasmic reticulum stress may alleviate the thyroid damage caused by depleted uranium.
作者
舒畅
赵雅贞
李杰
焦露
柳随义
李勇
李娟
冉永红
郝玉徽
SHU Chang;ZHAO Ya-zhen;LI Jie;QIAO Lu;LIU Sui-yi;LI Yong;LI Juan;RAN Yong-hong;HAO Yu-hui(Institute of Compound Injury,Department of Military Preventive Medicine,Army Medical University,Chongqing 400038,China)
出处
《局解手术学杂志》
2023年第3期192-196,共5页
Journal of Regional Anatomy and Operative Surgery
基金
国家自然科学基金项目(81972972)
军队后勤科研重点项目(BLJ20J005)。
关键词
贫铀
内质网应激
甲状腺
细胞凋亡
depleted uranium
endoplasmic reticulum stress
thyroid
apoptosis