FGF-21抑制HSC-T6细胞活化的抗肝纤维化作用及其机制的研究  

Effect of Fibroblast Growth Factor 21 on Hepatic Stellate Cell-T6 and Its Mechanism

作　　者：闫小敏 王大秀 王楠 李旭辉[3] 杨小明[1] 孟宪红[1] 胡凤丽[1] 韩继武[1] YAN Xiao-min;WANG Da-xiu;WANG Nan;LI Xu-hui;YANG Xiao-ming;MENG Xian-hong;HU Feng-li;HAN Ji-wu(Department of Gastroenterology,The fourth Affiliated Hospital of Harbin Medical University,Harbin,Heilongjiang,150001,China;College of Life Sciences,Northeast Agricultural University,Harbin,Heilongjiang,150030,China;Heilongjiang province the Red Coss Hospital(Heilongjiang province Forestry General Hospital,Harbin,Heilongjiang,150040,China)

机构地区：[1]哈尔滨医科大学附属第四医院消化内科,黑龙江哈尔滨150001 [2]东北农业大学生命科学学院,黑龙江哈尔滨150030 [3]黑龙江省红十字医院(黑龙江省森工总医院),黑龙江哈尔滨150040

出　　处：《现代生物医学进展》2019年第11期2076-2080,2060,共6页Progress in Modern Biomedicine

基　　金：黑龙江省教育厅科技研究面上项目(12521357)

摘　　要：目的:探索成纤维细胞生长因子21(FGF-21)对肝星形细胞T6(HSC-T6)活化的作用及其作用机制。方法:1640+10%胎牛血清的培养基培养HSC-T6细胞,实验分为5组:正常对照组(Control)、模型组(Model 20 m M乙醇处理细胞12 h)、低剂量FGF-21组(LFGF-21,0.5μmol/L)、中剂量FGF-21组(MFGF-21,1.0μmol/L)和高剂量FGF-21组(HFGF-21,2.0μmol/L)。Real-time PCR检测α-平滑肌肌动蛋白(α-SMA)、胶原蛋白Ⅰ(CollagenⅠ)、基质金属蛋白酶-2(MMP2)、基质金属蛋白酶-9(MMP9)和Notch2的m RNA水平,Western blot检测CollagenⅠ、α-SMA、MMP2、MMP9和Notch2的蛋白水平,ELISA检测IL-1β、TNF-α的蛋白水平。结果:模型组α-SMA、CollagenⅠ、MMP2、MMP9、IL-1β、TNF-α、Notch2的水平高于对照组(P<0.05),HFGF-21组α-SMA、CollagenⅠ、MMP2、MMP9、IL-1β、TNF-α、Notch2的水平均低于模型组(P<0.05)。结论:FGF-21可抑制Notch2的表达,抑制炎症反应,从而抑制HSC的活化,发挥抗肝纤维化作用。Objective: To investigate the effect of fibroblast growth factor 21(FGF-21) on hepatic stellate cell-T6(HSC-T6) and the mechanism of its action. Methods: Culturing HSC-T6 with 1640 medium supplemented with 10% fetal bovine serum and 1%antibiotics(penicillin-streptomycin). HSC-T6 were randomly divided into five groups: control group, model group(20 m M, ethanol), low dose FGF-21(LFGF-21, 0.5 μmol/L), middle dose FGF-21(MFGF-21, 1.0 μmol/L) and high dose FGF-21(HFGF-21, 2.0 μmol/L). The m RNA contents of α-SMA, CollagenⅠ, MMP2, MMP9 and Notch2 were determined by Real-time PCR. The protein levels of α-SMA, CollagenⅠ, MMP2, MMP9 and Notch2 were determined by Western blot. The protein levels of IL-1β and TNF-α were measured by ELISA kit. Results: The levels of α-SMA, CollagenⅠ, MMP2, MMP9, IL-1β, TNF-α and Notch2 in the model group were significantly higher than those in the control group(P<0.05), and those in the treatment group decreased significantly compared with the model group(P<0.05).Conclusion: FGF-21 can inhibit the expression of Notch2 and inflammation, and then inhibit HSC activation to attenuate hepatic fibrogenesis.

关 键 词：成纤维细胞生长因子21 肝纤维化 NOTCH2 炎症反应 

分 类 号：R-33[医药卫生] R575.2