基于TLR4/NF-κB/NLRP3信号通路探究白芍总苷对自身免疫性甲状腺炎大鼠炎症损伤的影响  

Effects of total glucosides of paeony on inflammatory injury in autoimmune thyroiditis rats based on TLR4/NF-κB/NLRP3 pathway

作　　者：吴苏豫[1] 王海涛[2] 张杨[3] 赵建林[1] 陈玉凤[1] 李江雁[1] 随华[1] 周艳红[1] WU Su-yu;WANG Hai-tao;ZHANG Yang;ZHAO Jian-lin;CHEN Yu-feng;LI Jiang-yan;SUI Hua;ZHOU Yan-hong(Dept of Endocrinology,Xinxiang Central Hospital,Xinxiang,Henan 453000,China;School of Health and Management,Xinxiang Medical University,Xinxiang,Henan 453003,China;School of Basic Medicine,Xinxiang Medical University,Xinxiang,Henan 453003,China)

机构地区：[1]新乡市中心医院内分泌科,河南新乡453000 [2]新乡医学院卫生健康管理学院,河南郑州453003 [3]新乡医学院基础医学院,河南郑州453003

出　　处：《中国药理学通报》2024年第8期1495-1500,共6页Chinese Pharmacological Bulletin

基　　金：河南省高等学校重点科研项目计划(No.20B320018)。

摘　　要：目的探讨白芍总苷对自身免疫性甲状腺炎(AIT)大鼠炎症损伤及TLR4/NF-κB/NLRP3通路的影响。方法实验分为对照组(Control)、模型组(Model)、白芍总苷组(TGP)、TLR4抑制剂组(TLR4 inhibitor)和TGP+TLR4激动剂组(TGP+TLR4 agonist),每组各10只。除Control组外,其余各组大鼠采用皮下注射甲状腺球蛋白与弗氏佐剂诱导AIT大鼠模型。给药6周后,苏木精-伊红(HE)染色观察甲状腺组织病理学变化;酶联免疫吸附法(ELISA)测定血清TPOAb、TgAb、TSH、T3、T4、TNF-α、INF-γ、IL-1β、IL-18水平;RT-qPCR和Western blot检测甲状腺组织TLR4/NF-κB/NLRP3信号通路mRNA和蛋白表达。结果与Control组相比,Model组大鼠甲状腺滤泡上皮明显受损,TPOAb、TgAb、TSH、T3、T4、TNF-α、INF-γ、IL-1β、IL-18水平升高(P<0.01),TLR4/NF-κB/NLRP3信号通路mRNA和蛋白表达升高(P<0.01)。与Model组相比,TGP组、TLR4 inhibitor组大鼠甲状腺滤泡上皮损伤减轻,TPOAb、TgAb、TSH、T3、T4、TNF-α、INF-γ、IL-1β、IL-18水平降低(P<0.01),TLR4/NF-κB/NLRP3信号通路mRNA和蛋白表达降低(P<0.01)。与TGP组相比,TGP+TLR4 agonist组大鼠甲状腺滤泡上皮损伤加重,TPOAb、TgAb、TSH、T3、T4、TNF-α、INF-γ、IL-1β、IL-18水平升高(P<0.05或P<0.01),TLR4/NF-κB/NLRP3信号通路mRNA和蛋白表达增加(P<0.05或P<0.01)。结论TGP通过抑制TLR4/NF-κB/NLRP3信号通路,改善甲状腺组织炎症损伤发挥甲状腺保护作用。Aim To investigate the effect of total glucosides of paeony on inflammatory injury and TLR4/NF-κB/NLRP3 pathway in autoimmune thyroiditis(AIT)rats.Methods The experiment was divided into control group,model group,total glucosides of paeony(TGP),TLR4 inhibitor group and TGP+TLR4 agonist group,with 10 animals in each group.Except for the control group,the rats in other groups were subcutaneously injected with thyroglobulin and Freund's adjuvant to induce the AIT rat model.After six weeks of administration,thyroid histopathological changes were observed using hematoxylin-eosin(HE)staining;serum levels of TPOAb,TgAb,TSH,T3,T4,TNF-α,INF-γ,IL-1βand IL-1βwere detected by enzyme-linked immunosorbent assay(ELISA);TLR4/NF-κB/NLRP3 pathway mRNAs and proteins expression in thyroid tissues were detected by RT-qPCR and Western blot.Results Compared with the control group,the thyroid follicular epithelium of rats was significantly damaged,and the serum levels of TPOAb,TgAb,TSH,T3,T4,TNF-α,INF-γ,IL-1βand IL-1βincreased(P<0.01).The expression of TLR4/NF-κB/NLRP3 pathway mRNAs and proteins increased in the model group(P<0.01).Compared with the model group,the damage of thyroid follicular epithelium was alleviated,and the serum levels of TPOAb,TgAb,TSH,T3,T4,TNF-α,INF-γ,IL-1βand IL-1βwere reduced(P<0.01),the expression of TLR4/NF-κB/NLRP3 pathway mRNAs and proteins were down-regulated in the TGP group and TLR4 inhibitor group(P<0.01).Compared with TGP group,the damage of thyroid follicular epithelium was aggravated,and the levels of serum TPOAb,TgAb,TSH,T3,T4,TNF-α,INF-γ,IL-1βand IL-1βwere elevated(P<0.05 or P<0.01),the protein expressions of TLR4/NF-κB/NLRP3 pathway mRNAs and proteins were up-regulated in TGP+TLR4 agonist group(P<0.05 or P<0.01).Conclusions TGP may play a protective role in thyroid by inhibiting the TLR4/NF-κB/NLRP3 pathway and improving the inflammatory injury of thyroid tissues.

关 键 词：白芍总苷 自身免疫性甲状腺炎 炎症损伤 TLR4/NF-κB/NLRP3通路 大鼠 甲状腺 

分 类 号：R-332[医药卫生] R284.1R322.51R364.5R581.4