利莫那班对肝星状细胞增殖和凋亡的影响及作用机制的开题报告.pdf

利莫那班对肝星状细胞增殖和凋亡的影响及作用机

制的开题报告

摘要

肝星状细胞是髓样细胞系的一种，是肝脏纤维化、肝硬化和肝癌等

疾病的重要细胞类型。利莫那班是一种免疫抑制剂，已被用于预防器官

移植排斥反应和治疗自身免疫性疾病等。本文通过综合阐述近年来利莫

那班对肝星状细胞增殖和凋亡的影响及其作用机制的文献资料，总结出

以下几个方面的研究进展：1.利莫那班可有效地抑制肝星状细胞增殖，降

低肝脏纤维化程度；2.利莫那班可以通过调节肝星状细胞增殖相关蛋白表

达，阻断PI3K/Akt/mTOR和ERK1/2等信号通路，从而抑制细胞增殖；3.

利莫那班还可以促进肝星状细胞凋亡，降低肝脏纤维化程度；4.利莫那班

可以调节NF-κB信号通路，抑制炎症因子的产生和释放，进而降低肝星

状细胞的活性，减轻肝损伤

关键词：利莫那班，肝星状细胞，增殖，凋亡，作用机制

Introduction

Hepaticstellatecells(HSCs)areatypeofmesenchymalcells

locatedinthespaceofDisseinliver,whichplayacrucialroleinthe

pathogenesisofliverfibrosis,cirrhosisandcancer(1).

Immunosuppressivetherapyhasbeenwidelyusedtopreventthe

rejectionoforgantransplantationandtotreatautoimmunediseases,

andamongthem,leflunomide(LEF)hasattractedmoreandmore

attentionduetoitseffectivenessinthetreatmentofHSCsactivation

andliverfibrosis(2).

Inthisreview,wesummarizetherecentstudiesontheeffectsof

LEFontheproliferationandapoptosisofHSCsanditsunderlying

mechanisms.

EffectsofLEFonHSCproliferation

LEFcaneffectivelyinhibittheproliferationofHSCs(3).Studies

haveshownthatLEFcandown-regulatetheexpressionofproliferation-

relatedproteinssuchascyclinD1andPCNA,andinhibittheactivation

ofthePI3K/Akt/mTORandERK1/2signalingpathways(4).These

findingssuggestthatLEFmayblockthecellcycleofHSCsandinhibit

theirproliferation.

EffectsofLEFonHSCapoptosis

LEFcanalsopromotetheapoptosisofHSCs(5).Studieshave

confirmedthatLEFcanup-regulatetheexpressionofBaxanddown-

regulatetheexpressionofBcl-2,andpromotetheactivationofcaspase-

3,thusinducingtheapoptosisofHSCs(6).Inaddition,LEFcanactivate

theNF-κBpathway,whichinhibitstheproductionandreleaseof

inflammatorycytokinesbyHSCs,reducestheiractivity,andthus

alleviatesliverdam