探索西罗莫司对斑马鱼胚胎模型生长发育的影响  

Exploring the effects of sirolimus on the growth and development of zebrafish embryo models

作　　者：张梓欣 邱桐 周江元 张学鹏 龚雪 杨开颖 兰钰茹 陈思源[2] 吉毅[1] ZHANG Zi-xin;QIU Tong;ZHOU Jiang-yuan;ZHANG Xue-peng;GONG Xue;YANG Kai-ying;LAN Yu-ru;CHEN Si-yuan;JI Yi(Dept of Pediatric Surgery,West China Hospital of Sichuan University,Chengdu 610041,China;Dept of Critical Care Medicine,West China Hospital of Sichuan University,Chengdu 610041,China)

机构地区：[1]四川大学华西医院小儿外科,四川成都610041 [2]四川大学华西医院重症医学科,四川成都610041

出　　处：《中国药理学通报》2024年第12期2368-2374,共7页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 82273556);四川省科技厅重点研发项目(No 2022 YFS0233,2022 YFS0225)。

摘　　要：目的通过斑马鱼模型探索西罗莫司对运动、血管、神经系统以及免疫系统生长发育的影响。方法斑马鱼胚胎受精后3 h,使用不同浓度的西罗莫司干预,记录胚胎的生长发育情况,并使用标记血管、神经、免疫细胞的转基因斑马鱼模型,对比药物对血管、神经、免疫系统生长发育的影响。结果浓度为0.5μmol·L^(-1)时,胚胎的孵化率明显降低,幼鱼的体长明显短于对照组(P<0.01),运动也明显减缓,幼鱼神经系统轴突的长度、节间血管的发育以及免疫细胞的生长发育都明显延迟,但浓度低于0.1μmol·L^(-1)时药物的影响差异无统计学意义。结论当西罗莫司超过一定浓度时,会明显减缓斑马鱼胚胎运动、血管、神经系统以及免疫系统的生长发育。因此,在使用西罗莫司治疗儿童疾病时,需要精准地监测血药浓度水平。Aim To explore the effects of sirolimus on the growth and development of motor,vascular,nervous,and immune systems through zebrafish models.Methods After 3 hours of fertilization of zebrafish embryos,different concentrations of sirolimus were added to the growth environment,and the growth and development of the embryos was recorded.Transgenic zebrafish models labeled with blood vessels,nerves or immune cells were used to compare the drug effects on the growth and development of those systems.Results At the concentration of 0.5μmol·L^(-1),the hatching rate and the body length(P<0.01)were significantly smaller than those of the control group,and movement was also significantly slowed down.Meanwhile,the length of axons of the nervous system,the development of intersegmental vessels,and the growth of immune cells were significantly delayed by drug treatment.But when the concentration was below 0.1μmol·L^(-1),there was no statistically difference between the control group and the sirolimus group.Conclusions When the concentration of sirolimus exceeds a certain level,it can significantly slow down the growth and development of movement,blood vessels,nervous system and immune system of zebrafish.Therefore,in clinical practice,it is important to monitor the blood concentration of sirolimus in children on time.

关 键 词：西罗莫司 生长发育 毒性 斑马鱼 胚胎 血药浓度 

分 类 号：R-332[医药卫生] R321R916.4R969.1R996