基于NOD1/RIP2/NF-κB信号通路探讨丹参酮ⅡA对复发性流产小鼠子宫母胎界面免疫状态的影响  

Effect of tanshinoneⅡA on immune status of uterine maternal-fetal interface in mice with recurrent spontaneous abortion based on NOD1/RIP2/NF-κB signaling pathway

作　　者：黄露[1] 黄海珍 HUANG Lu;HUANG Haizhen(Department of Obstetrics and Gynecology,Guangzhou Development Zone Hospital,Guangzhou 510730,Guangdong,China)

机构地区：[1]广州开发区医院妇产科,广东广州510730

出　　处：《贵州医科大学学报》2025年第3期405-410,416,共7页Journal of Guizhou Medical University

基　　金：广东省医学科学技术研究基金项目(20211116223930223)。

摘　　要：目的探讨丹参酮ⅡA调控含核苷酸结合寡聚化域蛋白1(nucleotide binding oligomerization domain containing protein 1,NOD1)/受体相互作用蛋白2(receptor-interacting protein 2,RIP2)/核因子-κB(nuclear transcription factor-κB,NF-κB)通路对复发性流产(recurrent spontaneous abortion,RSA)小鼠子宫母胎界面免疫状态的影响。方法雌性CBA/J小鼠随机分为对照组、RSA组、丹参酮ⅡA低浓度组、丹参酮ⅡA高浓度组、地屈孕酮组及丹参酮ⅡA高浓度+NOD1激活剂组(TriDAP),每组12只;于每日清晨对各组小鼠进行给药处理,处理14 d后,将动情期的对照组CBA/J小鼠与BALB/c小鼠按2∶1合笼构建正常妊娠,其它组CBA/J小鼠与DBA/2小鼠按2∶1合笼构建RSA模型,次日以小鼠阴道涂片出现大量精子且阴道口大开记为妊娠第1天,各组小鼠继续给药处理直至妊娠第10天;末次处理24 h后,检测小鼠胚胎丢失率,HE染色检测子宫蜕膜组织病理;取母胎界面组织,流式细胞术检测辅助性T细胞(helper T cell,Th)1、Th2占比及Th1/Th2比例,ELISA检测γ-干扰素(interferon-γ,IFN-γ)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)及白细胞介素-10(interleukin-10,IL-10)、IL-4水平,Western blot检测NOD1、RIP2、NF-κB p65蛋白表达水平。结果与对照组比较,RSA组小鼠子宫蜕膜组织显示排列紊乱的单个细胞数量减少,部分细胞核凝聚,细胞质染色不均匀,细胞间质水肿明显,血管数减少,胚胎丢失率、母胎界面组织中Th1占比、Th1/Th2比例、IFN-γ、TNF-α水平及NOD1、RIP2、NF-κB p65蛋白升高,母胎界面组织中Th2占比、IL-10、IL-4水平降低(P<0.05);与RSA组比较,丹参酮ⅡA低浓度组、丹参酮ⅡA高浓度组、地屈孕酮组小鼠子宫蜕膜组织病理损伤有所改善,胚胎丢失率、母胎界面组织中Th1占比、Th1/Th2比例、IFN-γ、TNF-α水平及NOD1、RIP2、NF-κB p65蛋白降低,母胎界面组织中Th2占比、IL-10、IL-4水平升高(P<0.05);TriDAP逆转了高浓�Objective To explore the effect of tanshinoneⅡA-regulated nucleotide-binding oligomerization domain-containing protein 1(NOD1)/receptor-interacting protein 2(RIP2)/nuclear transcription factorκB(NF-κB)pathway on the immune status of maternal-fetal interface in mice with recurrent spontaneous abortion(RSA).Methods Female CBA/J mice were grouped into the following groups:control,RSA,low concentration tanshinoneⅡA,high concentration tanshinoneⅡA,dydrogesterone and high concentration TanshinoneⅡA+NOD1 activator(TriDAP),with 12 mice in each group.The mice in each group were daily administered with medication at 8∶00 am.After 14 days of treatment,CBA/J mice in control group during estrus were co-caged with BALB/c mice at a 2∶1 ratio for normal breeding.CBA/J mice in other groups were co-caged with DBA/2 mice at a 2∶1 ratio to construct a RSA model.The first day of pregnancy was defined as the next day after a large number of sperm appeared on the vaginal smear of mice and the vaginal opening was wide open.The mice in each group were continuously to receive medication treatment until the 10th day of pregnancy.At 24 h after the last treatment,the loss rate of mouse embryos was examined.HE staining was applied to detect the pathology of endometrial tissue.Maternal-fetal interface tissues were collected.Flow cytometry was used to detect helper T cell(Th)1,Th2 proportion,and Th1/Th2 ratio.ELISA was used to detect the levels of interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),interleukin-10(IL-10),and IL-4.Western blot was applied to detect protein expressions of NOD1,RIP2,and NF-κB p65.Results When compared to control group,mouse uterine decidua tissue in RSA group exhibited decreased number of disordered individual cells,partial nuclear condensation,uneven cytoplasmic staining,obvious interstitial edema,reduced blood vessel number.RSA group had elevated embryo loss rate relative to control group.The proportion of Th1,Th1/Th2 ratio,the levels of IFN-γ,TNF-α,NOD1,RIP2,and NF-κB p65 proteins were hig

关 键 词：丹参酮ⅡA 复发性流产 母胎界面 免疫 TH1/TH2 

分 类 号：R285.5[医药卫生—中药学]