| 155 | 0 | 59 |
| 下载次数 | 被引频次 | 阅读次数 |
目的 通过体外试验探讨特女贞苷抗肝纤维化的作用机制。方法 应用10 ng/mL转化生长因子β(trans-forming growth factor beta, TGF-β)诱导大鼠肝星状细胞系(HSC-T6)2 h,用不同浓度特女贞苷(0～100μmol/L)处理HSC-T6细胞24 h;通过Western blot、RT-qPCR、细胞免疫荧光等方法检测HSC-T6细胞中TLR2、TLR4、α-SMA、Collagen-I表达情况，明确特女贞苷调节TLR2/TLR4信号通路抑制HSC-T6的作用机制。结果 TGF-β成功诱导HSC-T6细胞活化，特女贞苷能明显下调α-SMA、Collagen-I、TLR2、TLR4蛋白和mRNA表达，TGF-β诱导HSC-T6细胞活化可被特女贞苷通过调节TLR2/TLR4信号通路有效阻断。结论 特女贞苷能有效抑制细胞外基质(ECM)产生，调节肝纤维化，作用机制可能与抑制TLR2/TLR4信号通路有关。
Abstract：Objective To investigate the mechanism of specnuezhenide in alleviating hepatic fibrogenesis through in vitro experiments.Methods The rat hepatic stellate cell line(HSC-T6) was induced with 10 ng/mL transform-ing growth factor beta(TGF-β) for 2 h, and different concentrations of specnuezhenide(0-100 μmol/L)were administered to the HSC-T6 cells for 24 h, and the expression levels of TLR2,TLR4,α-SMA,and Collagen-I in the HSC-T6 cells were detected by Western blot, RT-qPCR,immunofluorescence and other methods.These experiments aimed to elucidate the mechanism by which specnuezhenide inhibits HSC-T6 activation via modulation of the TLR2/TLR4 signaling pathway.Results TGF-β successfully induced HSC-T6 cell activation, while specnuezhenide significantly downregulated the expression of α-SMA,Collagen-I,TLR2,and TLR4 at both protein and mRNA levels.Furthermore, specnuezhenide effectively blocked TGF-β induced HSC-T6 activation by modulating the TLR2/TLR4 signaling pathway.Conclusion Specnuezhenide can effectively inhibit the production of extracellular matrix(ECM) to regulate hepatic fibrogenesis, and its mechanism of action may be related to the inhibition of the TLR2/TLR4 signaling pathway.
[1] GRESSNER A M,WEISKIRCHEN R,BREITKOPF K,et al.Roles of TGF-beta in hepatic fibrosise[J].Frontiers in Bioscience,2022,7(1):793-807.
[2] JIANG Min,CUI Benwen,WU Yanling,et al.P2X7R orchestrates the progression of murine hepatic fibrosis by making a feedback loop from macrophage to hepatic stellate cells[J].Toxicology Letters,2020,333:22-32.
[3] LODDER J,DENA?S T,CHOBERT M N,et al.Macro- phage autophagy protects against liver fibrosis in mice[J].Autophagy,2015,11(8):1280-1292.
[4] ROH Y S,ZHANG Bi,LOOMBA R,et al.TLR2 and TLR9 contribute to alcohol-mediated liver injury through induction of CXCL1 and neutrophil infiltration[J].Ameri- can Journal of Physiology-Gastrointestinal and Liver Phy- siology,2015,309(1):30-41.
[5] SEKI E,DE MINICIS S,OSTERREICHER C H,et al.TLR4 enhances TGF-beta signaling and hepatic fibrosise[J].Nature Medicine,2007,13(11):1324-1332.
[6] MOKHTARI Y,POURBAGHERI-SIGAROODI A,ZAFARI P,et al.Toll-like receptors (TLRs):An old family of im- mune receptors with a new face in cancer pathogenesis[J].Journal of Cellular and Molecular Medicine,2021,25(2):639-651.
[7] ALBRECHT V,HOFER T P J,FOXWELL B,et al.Tolerance induced via TLR2 and TLR4 in human dendritic cells:Role of IRAK-1[J].BMC Immunology,2008,9:69.
[8] DEANGELIS R A,MARKIEWSKI M M,LAMBRIS J D.Liver regeneration:A link to inflammation through complement[J].Advances in Experimental Medicine and Biology,2006,586:17-34.
[9] BRUBAKER S W,BONHAM K S,ZANONI I,et al.Innate immune pattern recognition:A cell biological perspective[J].Annual Review of Immunology,2015,33:257-290.
[10] LEE U E,FRIEDMAN S L.Mechanisms of hepatic fibrogenesis[J].Best Practice & Research Clinical Gastroenterology,2011,25(2):195-206.
[11] ZHOU Wence,ZHANG Quanbao,QIAO Liang.Pathogenesis of liver cirrhosis[J].World Journal of Gastroenterology,2014,20(23):7312-7324.
[12] SCHUPPAN D,AFDHAL N H.Liver cirrhosise[J].The Lancet,2008,371(9615):838-851.
[13] BAHR M J,OCKENGA J,B?KER K H,et al.Elevated resistin levels in cirrhosis are associated with the proinflammatory state and altered hepatic glucose metabolism but not with insulin resistance[J].American Journal of Physiology-Endocrinology and Metabolism,2006,291(2):199-206.
[14] LEE H K,DUNZENDORFER S,TOBIAS P S.Cytoplas- mic domain-mediated dimerizations of toll-like receptor 4 observed by beta-lactamase enzyme fragment complementa- tion[J].Journal of Biological Chemistry,2004,279(11):10564-10574.
[15] PARK B S,LEE J O.Recognition of lipopolysaccharide pattern by TLR4 complexes[J].Experimental & Molecu- lar Medicine,2013,45(12):66.
[16] AKSOY E,TABOUBI S,TORRES D,et al.The p110δ isoform of the kinase PI(3)K controls the subcellular compartmentalization of TLR4 signaling and protects from endotoxic shock[J].Nature Immunology,2012,13:1045-1054.
[17] ZHANG Haifeng,TAY P N,CAO Weiping,et al.Integrin-nucleated Toll-like receptor (TLR) dimerization reveals subcellular targeting of TLRs and distinct mechanisms of TLR4 activation and signaling[J].FEBS Letters,2002,532(1/2):171-176.
[18] YIM M.The role of Toll-like receptors in osteoclastogene- sis[J].Journal of Bone Metabolism,2020,27(4):227-235.
[19] MUKHERJEE S,PATRA R,BEHZADI P,et al.Toll-like receptor-guided therapeutic intervention of human cancers:Molecular and immunological perspectives[J].Frontiers in Immunology,2023,14:1244345.
基本信息:
中图分类号:R285.5
引用信息:
[1]冯亓垣,刘官成,孙海明,等.特女贞苷调节TLR2/TLR4信号通路抑制肝纤维化的作用机制[J].北华大学学报(自然科学版),2025,26(06):751-755.
基金信息:
国家自然科学基金项目(82304848)
2025-10-27
2025-10-27
2025-10-27