HMGB1通过TLR4/NF-κB/NLRP3信号通路介导内皮细胞焦亡在系统性血管炎中的作用机制  

Mechanism of Endothelial Pyrodeath Mediated by HMGB1 in Systemic Vasculitis Via TLR4/NF-κB/NLRP3 Signaling Pathway

作　　者：秦影 李新 史丽东 刘扬洋 王智慧 关岳 QIN Ying;LI Xin;SHI Lidong;LIU Yangyang;WANG Zhihui;GUAN Yue(Department of Rheumatology and Immunology,the Third Affiliated Hospital of Qiqihar Medical College,Qiqihar,Heilongjiang Province,161006 China;Department of Emergency Internal Medicine,the Third Affiliated Hospital of Qiqihar Medical College,Qiqihar,Heilongjiang Province,161006 China)

机构地区：[1]黑龙江省齐齐哈尔医学院附属第三医院风湿免疫科,黑龙江齐齐哈尔161006 [2]黑龙江省齐齐哈尔医学院附属第三医院急诊内科,黑龙江齐齐哈尔161006

出　　处：《系统医学》2024年第11期26-29,共4页Systems Medicine

基　　金：2022年黑龙江省卫生健康委医药卫生科研课题(20220303100648)。

摘　　要：目的探究高迁移率族蛋白1(High Mobility Group Box Protein1, HMGB1)通过(Toll-like Receptor4,TLR4)/核因子κB(Nuclear Factor Kappa-B, NF-κB)/NOD样受体热蛋白结构域相关蛋白3(NOD-like Receptor Thermal Protein Domain Associated Protein 3, NLRP3)信号通路介导内皮细胞焦亡在系统性血管炎中的作用机制。方法 研究于2021年10月—2023年9月在齐齐哈尔医学院附属第三医院开展。取人脐静脉血管内皮细胞进行培养,随机分为对照组和实验组,实验组加入人重组HMGB1,对比对照组与实验组、实验组NLRP3及TLR4表达抑制前后,内皮细胞焦亡相关蛋白的表达水平。结果 系统性血管炎组与健康对照组比较,人脐静脉血管内皮细胞中HMGB1、含半胱氨酸的天冬氨酸蛋白水解酶-1(caspase-1)、白细胞介素-1β(interleukin-1β, IL-1β)、白细胞介素-18(interleukin-18, IL-18)水平升高,差异有统计学意义(P均<0.05)。细胞实验中实验组与对照组比较,caspase-1、IL-1β、IL-18水平升高,差异有统计学意义(P均<0.05)。过表达HMGB1并抑制NLRP3可使NLRP3(2.71±0.59 vs 1.24±0.58)、caspase-1(0.69±0.12 vs 0.40±0.03)、IL-1β[(1.75±0.31)pg/mL vs (1.16±0.12)pg/mL]、IL-18[(0.15±0.04)pg/mL vs (0.09±0.01)pg/mL]水平降低,差异有统计学意义(P均<0.05);过表达HMGB1并抑制TLR4可使TLR4(4.93±1.04 vs 1.96±0.84)、NF-κB(5.62±1.39 vs 2.15±1.04)、NLRP3(2.71±0.59 vs 1.24±0.58)、caspase-1(0.69±0.12 vs 0.40±0.03)、IL-1β[(1.75±0.31)pg/mL vs (1.16±0.12)pg/mL]、IL-18[(0.15±0.04)pg/mL vs (0.09±0.01)pg/mL]水平明显降低,差异有统计学意义(P均<0.05)。结论 HMGB1通过调节TLR4/NF-κB/NLRP3信号通路介导内皮细胞焦亡,进而改善系统性血管炎。Objective To explore the mechanism of endothelial pyrodeath mediated by high mobility group box protein 1(HMGB1)through the toll-like receptor 4(TLR4)/nuclear factorκB(NF-κB)/nod-like receptor thermal protein do-main associated protein 3(NLRP3)signaling pathway in systemic vasculitis.Methods The study was conducted from October 2021 to September 2023 at the Third Affiliated Hospital of Qiqihar Medical College.Human umbilical vein endothelial cells were cultured and randomly divided into a control group and an experimental group.The experimen-tal group was supplemented with human recombinant HMGB1,and the expression levels of pyroptosis related proteins in endothelial cells were compared between the control group and the experimental group before and after NLRP3 and TLR4 inhibition.Results The levels of HMGB1,caspase-1,interleukin-1β(IL-1β),interleukin-18(IL-18)in hu-man umbilical vein endothelial cells were increased in systemic vasculitis group compared with healthy control group,and the differences were statistically significant(all P<0.05).The levels of caspase-1,IL-1βand IL-18 increased in the cell experiment compared with the control group,and the differences were statistically significant(P<0.05).Over-expression of HMGB1 and inhibition of NLRP3 resulted in NLRP3(2.71±0.59 vs 1.24±0.58),caspase-1(0.69±0.12 vs 0.40±0.03),IL-1β[(1.75±0.31)pg/mL vs(1.16±0.12)pg/mL],IL-18[(0.15±0.04)pg/mL vs(0.09±0.01)pg/mL]lev-els decreased,and the differences were statistically significant(all P<0.05).Overexpression of HMGB1 and inhibition of TLR4 induced TLR 4(4.93±1.04 vs 1.96±0.84),NF-κB(5.62±1.39 vs 2.15±1.04),NLRP3(2.71±0.59 vs 1.24±0.58),caspase-1(0.69±0.12 vs 0.40±0.03),IL-1β[(1.75±0.31)pg/mL vs(1.16±0.12)pg/mL],IL-18[(0.15±0.04)pg/mL vs(0.09±0.01)pg/mL]level decreased significantly,the differences were statistically significant(all P<0.05).Conclusion HMGB1 mediated endothelial pyrodeath by regulating the TLR4/NF-κB/NLRP3 signaling pathway,thereby ameliorating systemic vasculitis.

关 键 词：HMGB1 TLR4/NF-κB/NLRP3 内皮细胞焦亡 系统性血管炎 

分 类 号：R543[医药卫生—心血管疾病]