视网膜内源性多肽CKASK...氯联苯暴露致子代视网膜损伤_姜悦.pdf

东南大学学报(医学版)J Southeast Univ(Med Sci Edi)2023，Feb;42(1):15-21他汀减轻小鼠肠缺血再灌注损伤中的作用 J 中华麻醉学杂志，2021，41(6):685-689 12 WANG B W，JIANG Y，YAO Z L，et al Aucubin protectschondrocytes against IL-1-induced apoptosis in vitro and in-hibits osteoarthritis in mice model J Drug Des Devel Ther，2019，13(1):3529-3538 13JELEN L A，YOUNG A H，STONE J M Ketamine:a tale oftwo enantiomersJ J Psychopharmacol，2021，35(2):109-123 14WANG J，WANG Y，XU X，et al Use of various doses of S-ketamine in treatment of depression and pain in cervical Car-cinoma Patients with mild/moderate depression after laparo-scopic total hysterectomyJ Med Sci Monit，2020，26(1):e922028-e922032 15NOWAK W，GENDAS L N，SANMACO L M，et al Pro-in-flammatory monocyte profile in patients with major depressivedisorder and suicide behaviour and how ketamine induces an-ti-inflammatory M2 macrophages by NMDA and mTO J EBioMedicine，2019，50(1):290-305 16CHOW Y Y，CHIN K Y The role of inflammation in the path-ogenesis of osteoarthritis J Mediators Inflamm，2020，2020:8293921 17MEHANA E E，KHAFAGA A F，EL-BLEHI S S The role ofmatrix metalloproteinases in osteoarthritis pathogenesis:anupdated review J Life Sci，2019，234(1):116786-116794 18刘波，刘毅，熊华章，等 盐酸氨基葡萄糖对膝骨关节炎家兔 MMP-3、TIMP-1 的影响J 现代医学，2016，44(12):1741-1745 19陈小青，林金丁，张华昆，等 塞来昔布对骨关节炎大鼠模型抗炎镇痛作用研究 J 中国临床药理学杂志，2020，36(10):1315-1317 20SUN Q，ZHANG Y，DING Y，et al Inhibition of PGE2 in sub-chondral bone attenuates osteoarthritisJ Cells，2022，11(17):2760-2780 21GU M，JIN J，EN C，et al Akebia Saponin D suppresses in-flammation in chondrocytes via the NF2/HO-1/NF-B axisand ameliorates osteoarthritis in mice J Food Funct，2020，11(12):10852-10863 22CHEN Z，ZHONG H，WEI J，et al Inhibition of Nrf2/HO-1signaling leads to increased activation of the NLP3 inflam-masome in osteoarthritisJ Arthritis es Ther，2019，21(1):300-312 23KHAN N M，HASEEB A，ANSAI M Y，et al Wogonin，aplant derived small molecule，exerts potent anti-inflammatoryand chondroprotective effects through the activation of OS/EK/Nrf2 signaling pathways in human osteoarthritis chon-drocytes J Free adic Biol Med，2017，106(1):288-301 收稿日期2022-10-07修回日期2022-11-28 基金项目国家自然科学基金面上项目(81670900);南京市科技发展项目一般项目(YKK19115);南京医科大学科技发展基金一般项目(NMUB2020112)作者简介姜悦(1994 )，女，江苏宿迁人，住院医师，医学硕士。E-mail:jxyddu163 com 通信作者张昕E-mail:jsbyvelmaxinxin126 com 引文格式姜悦，李楠，李景云，等 视网膜内源性多肽 CKASKGKL 调节 p53/cyclinD1 信号通路拮抗多氯联苯暴露致子代视网膜损伤J 东南大学学报(医学版)，2023，42(1):15-21 论著 视网膜内源性多肽 CKASKGKL 调节 p53/cyclinD1信号通路拮抗多氯联苯暴露致子代视网膜损伤姜悦1，李楠2，李景云3，池霞1，童梅玲1，张昕1(1 南京医科大学附属妇产医院 儿童保健科，江苏 南京210004;2 宁波市第一医院 新生儿科，浙江 宁波315010;3 南京医科大学附属妇产医院 医学研究中心，江苏 南京210004)摘要目的:探讨视网膜内源性多肽 CKASKGKL 对多氯联苯(PCBs)暴露致子代视网膜发育异常的拮抗作用及可能的作用机制。方法:以斑马鱼为模式动物，收集斑马鱼胚胎予以 PCBs 处理，同时给予多肽 CK-51ASKGKL 进行挽救实验，收集受精后 48 h 幼鱼制备石蜡切片，显微镜下观察各组子代斑马鱼视网膜发育情况。以大鼠视网膜神经节细胞(GC)为工具细胞，予以 PCBs 处理，同时给予多肽 CKASKGKL 进行挽救实验，CCK-8 检测各组细胞增殖活性;采用基因富集分析(GSEA)了解多肽 CKASKGKL 可能作用的信号通路，Western blotting 初步验证多肽 CKASKGKL 对视网膜神经节细胞 p53/cyclinD1 信号通路的影响。结果:多肽CKASKGKL 可以拮抗 PCBs 暴露致子代斑马鱼视网膜发育异常，可以拮抗 PCBs 暴露致视网膜神经节细胞增殖活性降低;GSEA 结果显示，多肽 CKASKGKL 可能通过参与 p53 信号通路发挥作用;Western blotting 检测显示，多肽 CKASKGKL 干预后，视网膜神经节细胞中 p53 表达降低，其下游负调控基因 cyclinD1 表达增高。结论:多肽 CKASKGKL 可以拮抗 PCBs 暴露导致的子代视网膜损伤，可能与其通过调节 p53/cyclinD1 信号通路而促进细胞增殖有关。关键词内源性多肽;多氯联苯;视网膜发育;p53/cyclinD1 信号通路;斑马鱼;大鼠 中图分类号774 1 文献标志码A 文章编号1671-6264(2023)01-0015-07doi:10 3969/j issn 1671-6264 2023 01 003Endogenous retinal peptide CKASKGKL antagonizes retinal damagecaused by PCBs exposure in offspring by regulating p53/cyclinD1signaling pathwayJIANG Yue1，LI Nan2，LI Jingyun3，CHI Xia1，TONG Meiling1，ZHANG Xin1(1 Department of Child Health，Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University，Nanjing 210004，China;2 Department of Neonatology，the First Hospital of Ningbo，Ningbo 315010，China;3 Medical esearch Center，Obstetricsand Gynecology Hospital Affiliated to Nanjing Medical University，Nanjing 210004，China)AbstractObjective:To explore the antagonistic effect of endogenous retinal peptide CKASKGKL on offspringretinal dysplasia induced by PCBs and its possible mechanism Methods:Zebrafish were selected as model animal，embryos were collected and treated with PCBs，and CKASKGKL was treated to perform rescue experiment simulta-neously，the juveniles were collected to make paraffin sections 48 hours after fertilization，and the retina of zebrafishoffspring in each group was observed under microscope at retinal ganglion cells(GCs)were used as tool cells，treated with PCBs，at the same time treated with CKASKGKL for rescue experiment，and CCK-8 was used to detectthe proliferation activity of cells in each group Gene enrichment analysis(GSEA)method was used to analyze thesignaling pathways in which CKASKGKL might function，Western blotting was used to verify the effect of CK-ASKGKL on the p53/cyclinD1 signaling pathway in GCs preliminarily esults:CKASKGKL could antagonize theretinal dysplasia of zebrafish offspring caused by PCBs，and could antagonize the decrease of proliferation activity ofGCs caused by PCBs exposure The results of GSEA showed that CKASKGKL might play a role through p53 signa-