矢车菊水提物对grx细胞系的抗纤维化作用

Fabiana Garbachi de Oliveira Mendes Ouri, P. Caruso, Gabriela Silva, H. B. Dias, J. R. Marques, F. B. Nunes, P. M. Ferreira, Jarbas R. Oliveira
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引用次数: 2

摘要

肝纤维化是一种复杂的疾病,是由于结缔组织沉积导致组织修复不适当而引起的。当慢性病变影响肝脏时,再生反应失败,肝细胞被丰富的细胞外基质(ECM)所取代。ECM的产生和降解之间的不平衡将导致蛋白质的积累,从而改变正常的肝脏结构,从而改变其功能。ECM的主要来源是活化的肝星状细胞(HSC)。为了明确可能的治疗方法,本工作旨在评估紫杉树可能的抗纤维化作用。活化的HSC永生化系(GRX)的Cabrera。结果表明,在0.039和0.078 mg/mL浓度下,人马花水提物能够抑制细胞的生长和增殖。氧化应激评价方面,治疗组与对照组比较,差异无统计学意义。用OilRed-O (ORO)染色显示,处理5天后细胞内脂质含量有统计学意义的增加,对GRX从激活到静止状态的表型变化有体外作用。这些结果通过比色定量脂质含量证实。TGF-β1和胶原蛋白的生成,两组间差异无统计学意义。综上所述,箭状花水提物降低了GRX细胞的生长和增殖,诱导了激活型向静止型的逆转。细胞增殖既没有因坏死而减少,也没有因活化衰老而导致细胞凋亡。因此,我们的数据表明,提取物显示出抗纤维化作用,可能是通过激活表型逆转。
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Antifibrotic effect of Pluchea sagitallis (Lam.) cabrera aqueous extract in grx cell lineage
Liver fibrosis is a complex disease that is caused by inappropriate tissue repair due to the deposition of connective tissue. When a chronic lesion affects the liver, regenerative response fails and hepatocytes are replaced with abundant extracellular matrix (ECM). The imbalance between production and degradation of ECM will result in the accumulation of proteins that change normal liver architecture, and thus its functionality. The main source of ECM is the activated hepatic stellate cell (HSC). In order, to clarify possible therapeutic approaches to the disease, this work aimed to evaluate the possible antifibrotic action of Pluchea sagitallis (Lam.) Cabrera on an activated HSC immortalized lineage (GRX). Our results demonstrated that the P. sagittalis aqueous extract at 0.039 and 0.078 mg/mL concentrations was able to reduce cell growth and proliferation. Regarding to oxidative stress evaluation, there was no statistically significant difference between the treated group and the control. Staining with OilRed-O (ORO) showed a statistically significant increase in intracellular lipid content after 5 days of treatment, exerting in vitro effect on the GRX phenotypic change of activated towards the quiescent state. These results were confirmed by colorimetric quantification of lipid content. Regarding the TGF-β1 and collagen production, there were no statistically significant differences observed between the groups. In conclusion, the P. sagittalis aqueous extract reduces the growth and proliferation of GRX cells and induces the reversal of activated towards a quiescent phenotype. There was no decrease in cell proliferation either by necrosis or by apoptosis via activation of the senescence. Thus, our data suggest that the extract showed an antifibrotic effect, possibly by activating phenotype reversal.
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