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医学临床研究  2022, Vol. 39 Issue (2): 168-172    DOI: 10.3969/j.issn.1671-7171.2022.02.003
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穿心莲内酯和吡非尼酮联合给药对TGF-β1诱导的肝星状细胞活化的影响及作用机制
许光, 马体栋, 赵凡, 李碧香, 周崇高**
湖南省儿童医院新生儿外科,湖南 长沙 410007
Study on the Effect and Mechanism of Andrographolide Combined with Pirfenidone on the Activation of Hepatic Stellate Cells Induced by TGF-β1
XU Guang, MA Ti-dong, ZHAO Fan, et al
Department of Neonatal Surgery, Hunan Children's Hospital, Changsha Hunan 410007
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摘要 【目的】探讨穿心莲内酯(AG)联合吡非尼酮(PFD)对转化生长因子-β1(TGF-β1)诱导的人肝星状细胞LX-2活化的影响及作用机制。【方法】以LX-2作为研究对象,常规体外培养后分为Control组、TGF-β1组、AG组、PFD组、AG+PFD组。采用MTT法测定各组细胞活力,采用qRT-PCR检测各组纤维标志物和炎性标志物mRNA表达水平,采用Western blot 检测各组细胞中TGF-β/Smad信号通路相关蛋白表达水平。【结果】相对于TGF-β1组,AG组、PFD组和AG+PFD组中纤维标志物mRNA[α-平滑肌肌动蛋白(α-SMA) mRNA、Ⅰ型胶原蛋白(Collagen-Ⅰ)mRNA、结缔组织生长因子(CTGF)mRNA],炎性标志物mRNA[白细胞介素6(IL-6)mRNA、白细胞介素1β(IL-1β)mRNA、肿瘤坏死因子(TNF-α)mRNA]和TGF-β/Smad信号通路相关蛋白(p-Smad2、p-Smad3)显著下调(均P<0.05);相对于AG组、PFD组,AG+PFD组中Collagen-ⅠmRNA、CTGF mRNA、p-Smad2和p-Smad3表达水平显著下调(均P<0.05);相对于PFD组,AG+PFD组中α-SMA mRNA、IL-6 mRNA表达水平显著下调(均P<0.05)。【结论】与单一疗法相比,AG联合PFD对TGF-β1诱导的LX-2活化发挥了更好的抗肝纤维化作用,其作用机制可能与其调控TGF-β/Smad信号通路有关。
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关键词 肝/细胞学星形细胞转化生长因子β1吡啶酮类穿心莲内酯    
Abstract:【Objective】To investigate the effect of andrographolide (AG) combined with pirfenidone (PFD) on hepatic stellate cell activation induced by transforming growth factor-β1(TGF-β1) and its mechanism . 【Methods】 Hepatic stellate cells (LX-2) were used as the research object. After routine in vitro culture, they were divided into control group, TGF-β1 Group , AG group, PFD group and AG + PFD group. MTT assay was used to determine the cell viability of five groups, RT-PCR was used to detect the mRNA expression levels of fiber markers and inflammatory markers, and Western blot was used to detect the related protein expression level of TGF -β/ Smad signaling pathway cells in each group.【Results】 Compared with TGF- β1 group, fiber markers(α- SMA mRNA, Collagen-ⅠmRNA and CTGF mRNA) inflammatory marker (IL-1βmRNA, IL-6 mRNA and TNF- αmRNA) and TGF-β/ Smad signaling pathway related proteins (p-Smad2, p-smad3) of the AG group, the PFD group and the AG + PFD group were significantly down regulated (mean P<0.05); Compared with the PFD group, the expression levels of α- SMA mRNA and IL-6 mRNA in the AG + PFD group were significantly down regulated (mean P<0.05).【Conclusion】 Compared with monotherapy, AG combined with PFD therapy has significant effect on the activation of hepatic stellate cells induced by TGF-β1, and plays a better role in anti hepatic fibrosis, and its mechanism may be related to the regulation of TGF-β/ Smad signaling pathway.
Key wordsLiver/CY    Astrocytes    Transforming Growth Factor beta1    Pyridones    ANDROGRAPHOLIDE
收稿日期: 2022-01-10     
中图分类号:  R322.47  
基金资助:湖南省中医药科研计划项目(2020048);湖南省出生缺陷协同防治科技重大专项(2019SK1010)
通讯作者: **E-mail:zhouchonggao@sina.com   
引用本文:   
许光, 马体栋, 赵凡, 李碧香, 周崇高. 穿心莲内酯和吡非尼酮联合给药对TGF-β1诱导的肝星状细胞活化的影响及作用机制[J]. 医学临床研究, 2022, 39(2): 168-172.
XU Guang, MA Ti-dong, ZHAO Fan, et al. Study on the Effect and Mechanism of Andrographolide Combined with Pirfenidone on the Activation of Hepatic Stellate Cells Induced by TGF-β1. JOURNAL OF CLINICAL RESEARCH, 2022, 39(2): 168-172.
链接本文:  
http://journal07.magtech.org.cn/yxlcyj/CN/10.3969/j.issn.1671-7171.2022.02.003     或     http://journal07.magtech.org.cn/yxlcyj/CN/Y2022/V39/I2/168
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