Fasudil prevents liver fibrosis via activating natural killer cells and suppressing hepatic stellate cells  

作　　者：Qiu-Ju Han Yong-Liang Mu Hua-Jun Zhao Rong-Rong Zhao Quan-Juan Guo Yu-Hang Su Jian Zhang 

机构地区：[1]Institute of Immunopharmaceutical Sciences,School of Pharmaceutical Sciences,Shandong University,Jinan 250012,Shandong Province,China [2]Department of Emergency Surgery,Qilu Hospital of Shandong University,Jinan 250012,Shandong Province,China

出　　处：《World Journal of Gastroenterology》2021年第24期3581-3594,共14页世界胃肠病学杂志（英文版）

基　　金：Supported by The National Natural Science Foundation of China,No.81972694 and No.81972686.

摘　　要：BACKGROUND Fasudil,as a Ras homology family member A(RhoA)kinase inhibitor,is used to improve brain microcirculation and promote nerve regeneration clinically.Increasing evidence shows that Rho-kinase inhibition could improve liver fibrosis.AIM To evaluate the anti-fibrotic effects of Fasudil in a mouse model of liver fibrosis induced by thioacetamide(TAA).METHODS C57BL/6 mice were administered TAA once every 3 d for 12 times.At 1 wk after induction with TAA,Fasudil was intraperitoneally injected once a day for 3 wk,followed by hematoxylin and eosin staining,sirius red staining,western blotting,and quantitative polymerase chain reaction(qPCR),and immune cell activation was assayed by fluorescence-activated cell sorting.Furthermore,the effects of Fasudil on hepatic stellate cells and natural killer(NK)cells were assayed in vitro.RESULTS First,we found that TAA-induced liver injury was protected,and the positive area of sirius red staining and type I collagen deposition were significantly decreased by Fasudil treatment.Furthermore,western blot and qPCR assays showed that the levels of alpha smooth muscle actin(α-SMA),matrix metalloproteinase 2(MMP-2),MMP-9,and transforming growth factor beta 1(TGF-β1)were inhibited by Fasudil.Moreover,flow cytometry analysis revealed that NK cells were activated by Fasudil treatment in vivo and in vitro.Furthermore,Fasudil directly promoted the apoptosis and inhibited the proliferation of hepatic stellate cells by decreasingα-SMA and TGF-β1.CONCLUSION Fasudil inhibits liver fibrosis by activating NK cells and blocking hepatic stellate cell activation,thereby providing a feasible solution for the clinical treatment of liver fibrosis.

关 键 词：Liver fibrosis Natural killer cells FASUDIL Hepatic stellate cells 

分 类 号：R575.2[医药卫生—消化系统]