基于miRNA介导的NLRP3炎症小体活化探讨中医药在肝纤维化发生中作用的研究进展  

Research progress on role of traditional Chinese medicine in hepatic fibrosis based on miRNA-mediated activation of NLRP3 inflammasome

作　　者：郭新华 郑洋 王佳慧 王鸿红 罗淑娟 黄娜[2] 赵铁建 郑博文 梁馨云 吴日舟 任秋怡 GUO Xin-hua;ZHENG Yang;WANG Jia-hui;WANG Hong-hong;LUO Shu-juan;HUANG Na;ZHAO Tie-jian;ZHENG Bo-wen;LIANG Xin-yun;WU Ri-zhou;REN Qiu-yi(Department of Physiology,College of Basic Medicine,Guangxi University of Chinese Medicine,Nanning 530222,China;Department of Medicine,Faculty of Chinese Medicine Science,Guangxi University of Chinese Medicine,Nanning 530222,China)

机构地区：[1]广西中医药大学基础医学院生理教研室,广西南宁530222 [2]广西中医药大学赛恩斯新医药学院医学系,广西南宁530222

出　　处：《中国中药杂志》2022年第9期2409-2418,共10页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(81960751,81660705);广西自然科学基金青年基金项目(2020GXNSFBA297094);广西中青年教师科研基础能力提升项目(2020KY59009);广西壮瑶药重点实验室项目(GXZYZZ2019-1,GXZYZZ2020-07);广西中医药大学一流学科项目(2019XK141);广西中医药大学自治区级大学生创新创业训练项目(S202110600041);广西中医药大学青年基金项目(2020QN006)。

摘　　要：近年来,肝纤维化已成为国内外肝病领域的研究热点。微小RNA(microRNA,miRNA)介导的Nod样受体热蛋白结构域相关蛋白3(Nod-like receptor,pyrin domain containing 3,NLRP3)炎症小体活化在肝纤维化的发生中扮演着重要的角色。该文主要就miRNA介导的NLRP3炎症小体活化在肝纤维化发生中的作用进行2个方面的论述:一方面为不同的miRNA分子通过调控NLRP3炎症小体活化进而调控肝纤维化,包括微小RNA-350-3p(microRNA-350-3p,miR-350-3p)/白细胞介素-6(interleukin-6,IL-6)介导的信号转导和转录激活因子3(signal transducer and activator of transcription 3,STAT3)/c-myc信号通路、微小RNA-148a(microRNA-148a,miR-148a)经hedgehog信号通路诱导肝星状细胞的自噬与凋亡、微小RNA-155(microRNA-155,miR-155)经细胞因子信号转导抑制物1(suppressor of cytokine signaling-1,SOCS-1)自身负反馈调节调控NLRP3炎症小体的炎性复合、微小RNA-181a(microRNA-181a,miR-181a)介导丝裂原活化蛋白激酶(mitogen extracellular signal regulated kinase,MEK)/细胞外信号调节激酶(extracellular signal regulated kinase,ERK)/核转录因子κB(nuclear transcription factorκB,NF-κB)炎症通路活性调节下游NLRP3炎症通路激活、微小RNA-21(mircoRNA-21,miR-21)通过抑制肿瘤坏死因子α诱导蛋白3(tumor necrosis factor-αinducible protein 3,A20)促进小鼠RAW264.7细胞中NF-κB和NLRP3的表达、微小RNA-20b(microRNA-20b,miR-20b)可激活NLRP3信号通路进而促进白细胞介素-1β(interleukin-1β,IL-1β)、白细胞介素-18(interleukin-18,IL-18)炎症因子的表达等调控肝纤维化;另一方面为不同中医药基于miRNA介导的NLRP3炎症小体活化抗肝纤维化的效果,包括莪术、甘草、衢枳壳、虎杖、牡丹皮、白芍、淫羊藿、肉桂等中药活性成分调控肝纤维化的作用机制。In recent years,liver fibrosis has become a hotspot in the field of liver diseases.MicroRNA(miRNA)-mediated Nod-like receptor pyrin domain containing 3(NLRP3)inflammasome activation is pivotal in the pathogenesis of liver fibrosis.The present study mainly discussed the role of miRNA-mediated NLRP3 inflammasome activation in the pathogenesis of liver fibrosis.Different miRNA molecules regulated liver fibrosis by mediating NLRP3 inflammasome activation,including miRNA-350-3 p(miR-350-3 p)/interleukin-6(IL-6)-mediated signal transducer and activator of transcription 3(STAT3)/c-myc signaling pathway,miR-148 a-induced autophagy and apoptosis of hepatic stellate cells via hedgehog signaling pathway,miR-155-mediated NLRP3 inflammasome by the negative feedback of the suppressor of cytokine signaling-1(SOCS-1),miR-181 a-mediated downstream NLRP3 inflammatory pathway activation through mitogen-activated protein kinase kinase(MEK)/extracellular signal-regulated kinase(ERK)/nuclear transcription factorκB(NF-κB)inflammatory pathway,miR-21-promoted expression of NF-κB and NLRP3 of RAW264.7 cells in mice by inhibiting tumor necrosis factor-αinducible protein 3(A20),and miR-20 b-promoted expression of IL-1βand IL-18 by activating NLRP3 signaling pathway.Additionally,the anti-liver fibrosis mechanism of different active components in Chinese medicines(such as Curcumae Rhizoma,Glycyrrhizae Radix et Rhizoma,Aurantii Fructus,Polygoni Cuspidati Rhizoma et Radix,Moutan Cortex,Paeoniae Radix Alba,Epimedii Folium,and Cinnamomi Cortex)was also explored based on the anti-liver fibrosis effect of miRNA-mediated NLRP3 inflammasome activation.

关 键 词：MIRNA NLRP3炎症小体 肝纤维化 中医药 

分 类 号：R259[医药卫生—中西医结合]