基于TLR4信号通路的中药抗肝脏疾病作用研究进展
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摘要
肝脏疾病是发生在肝脏的所有疾病的总称。近年来中药在治疗肝脏疾病中有一定优势,其实验研究作用显著或临床应用疗效较好,不良反应较少,呈现了广阔的前景。Toll样受体4(TLR4)信号通路与肝脏疾病息息相关,其抑制机制是通过TLR4介导的信号通路活化核转录因子-κB(NF-κB),抑制白细胞介素-1β(IL-1β),白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)等炎症因子的分泌,抑制肝细胞的炎症损伤,进一步抑制了IL-1β,IL-6,TNF-α等对肝星状细胞(HSC)等细胞的激活,其阻断TRL4通路的方式为①抑制TLR4的表达;②抑制TLR4二聚体化;③阻断胞内信号转导,通过作用于衔接蛋白,作用于激酶IL-1受体相关激酶(IRAKs),作用于去泛素化酶锌指蛋白A20(TLRAFst)。通过这几个方面阻断TRL4通路,抑制炎症反应发生,达到抗肝脏疾病的作用。因此,抑制或增强TLR4信号通路或针对TLR4信号通路中某些环节进行干预成为肝病治疗的新策略。目前TLR4信号通路成为中药抗肝脏疾病的靶点之一。本文对近年中药抗TLR4信号通路活化,通过中药单体及有效部位、中药提取物、中药复方等发挥抗肝脏疾病作用的文献进行整理,为下一步中西医治疗肝脏疾病提供重要的指导意义和方向。
Liver disease is the general term for all diseases that occur in the liver. In recent years,traditional Chinese medicine has certain advantages in the treatment of liver diseases. With a high experimental study value,good clinical efficacy and less adverse reactions,it has broad prospects. Toll-like receptor 4( TLR4)signaling pathway is closely related to liver diseases. Its mechanism is to activate nuclear factor-κB( NF-κB)through tlr4-mediated signaling pathway,inhibit the secretion of such inflammatory factors as interleukin-1( IL-1),interleukin-6( IL-6) and tumor necrosis factor-alpha( TNF-α),and the inflammatory damage of liver cells,so as to further inhibit the effect of IL-1,IL-6,TNF-α in activating Hepatic Stellate Cell( HSC). The ways of blocking TRL4 pathway are as follows: Inhibiting the expression of TLR4,Inhibiting the dimerization of TLR4.Blocking intracellular signal transduction: ①acting on the binding protein; ②acting on the kinase IRAKs; ③acting on TLRAFst. In these ways,the TRL4 pathway is blocked,the inflammation is inhibited,and the anti-liver disease effect is achieved. Therefore,inhibiting or enhancing TLR4 signaling pathway or intervening in some links of TLR4 signaling pathway has become a new strategy for the treatment of liver diseases. Toll-like receptor 4 signaling pathway has become one of the targets of traditional Chinese medicine( TCM) against liver diseases. In this paper,the recent literatures on the effect of TCM in resisting activation of TLR4 signaling pathway and the effect of anti-liver diseases through monomers and effective parts of TCM,extracts of TCM and compound prescriptions of TCM were collected and summarized to provide important guiding significance and direction for the treatment of liver diseases by TCM and WM in the next step.
Liver disease is the general term for all diseases that occur in the liver. In recent years,traditional Chinese medicine has certain advantages in the treatment of liver diseases. With a high experimental study value,good clinical efficacy and less adverse reactions,it has broad prospects. Toll-like receptor 4( TLR4)signaling pathway is closely related to liver diseases. Its mechanism is to activate nuclear factor-κB( NF-κB)through tlr4-mediated signaling pathway,inhibit the secretion of such inflammatory factors as interleukin-1( IL-1),interleukin-6( IL-6) and tumor necrosis factor-alpha( TNF-α),and the inflammatory damage of liver cells,so as to further inhibit the effect of IL-1,IL-6,TNF-α in activating Hepatic Stellate Cell( HSC). The ways of blocking TRL4 pathway are as follows: Inhibiting the expression of TLR4,Inhibiting the dimerization of TLR4.Blocking intracellular signal transduction: ①acting on the binding protein; ②acting on the kinase IRAKs; ③acting on TLRAFst. In these ways,the TRL4 pathway is blocked,the inflammation is inhibited,and the anti-liver disease effect is achieved. Therefore,inhibiting or enhancing TLR4 signaling pathway or intervening in some links of TLR4 signaling pathway has become a new strategy for the treatment of liver diseases. Toll-like receptor 4 signaling pathway has become one of the targets of traditional Chinese medicine( TCM) against liver diseases. In this paper,the recent literatures on the effect of TCM in resisting activation of TLR4 signaling pathway and the effect of anti-liver diseases through monomers and effective parts of TCM,extracts of TCM and compound prescriptions of TCM were collected and summarized to provide important guiding significance and direction for the treatment of liver diseases by TCM and WM in the next step.
引文
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[5]吴涛,柳涛,郑培永,等.清肝活血方及其拆方对酒精性肝病大鼠CD14、TLR4表达的影响[J].世界华人消化杂志,2008,16(30):3372-3380.
[6] YUAN Y,XIA G, LI Z, et al. Chlorogenic acid ameliorated concanavalin A-induced hepatitis by suppression of Toll-like receptor 4 signaling in mice[J].Int Immunopharmacol,2017,44:97-104.
[7] ZHOU G Y,YI Y X,JIN L X,et al. The protective effect of juglanin on fructose-induced hepatitis by inhibiting inflammation and apoptosis through TLR4 and JAK2/STAT3 signaling pathways in fructose-fed rats[J]. Biomed Pharmacother,2016,81:318-328.
[8]王建青,李俊,邹宇宏,等.豹皮樟总黄酮对非酒精性脂肪性肝炎治疗作用及部分机制[J].中国药理学通报,2012,28(3):412-416.
[9] WANG G,HU Z,FU Q,et al. Resveratrol mitigates lipopolysaccharide-mediated acute inflammation in rats by inhibiting the TLR4/NF-κBp65/MAPKs signaling cascade[J]. Sci Rep,2017,doi:10. 1038/srep45006.
[10] WANG Y,LI B,ZHU J,et al. Lonicera caerulea berry extractsuppresseslipopolysaccharide-induced inflammation via Toll-like receptor and oxidative stressassociated mitogen-activated protein kinase signaling[J]. Food Funct,2016,7(10):4267-4277.
[11]龚毅,范伟,张莹,等.银杏叶提取物对大鼠非酒精性脂肪肝炎肝脏保护作用的研究[J].重庆医学,2015,44(30):4190-4192.
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