首页|莪术醇通过Sirt1-p53信号通路诱导肝星状细胞衰老减轻肝纤维化

莪术醇通过Sirt1-p53信号通路诱导肝星状细胞衰老减轻肝纤维化

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目的 探讨莪术醇对肝纤维化的治疗作用及其可能机制.方法 用不同浓度莪术醇5、10、15、20、30、45、60、80和100 μmol/L培养人肝星状细胞株HSC-LX2 24 h,采用CCK-8法检测细胞活力.选择三个浓度的莪术醇10、20、30μmol/L用于后续实验.Western blot法及免疫荧光实验检测肝纤维化相关蛋白α-平滑肌肌动蛋白(α-SMA)、α1(Ⅰ)胶原及纤连蛋白的表达;衰老相关-半乳糖苷酶(SA-β-Gal)染色检测衰老细胞;实时定量PCR检测衰老标志物p16、p21、高迁移率族蛋白A1(HMGA1)及端粒酶逆转录酶(TERT)mRNA表达;Western blot法检测沉默交配型信息调节因子2同源蛋白1(Sirt1)和p53蛋白表达.结果 与莪术醇0μmol/L比较,莪术醇20、30μmol/L处理后,α-SMA、α1(Ⅰ)胶原及纤连蛋白的表达下调,SA-β-Gal染色阳性细胞增加,p16、p21、HMGA1 mRNA表达和p53蛋白表达增加,TERT mRNA表达和Sirt1蛋白表达降低(P<0.05或P<0.01).加入Sirt1激动剂SRT 1720 5 μmol/L后,p16和p21 mRNA表达降低(P<0.01).结论 莪术醇能够通过Sirt1-p53信号通路诱导肝星状细胞衰老,从而减轻肝纤维化.
Curcumol alleviates hepatic fibrosis by inducing hepatic stellate cell senescence through Sirt1-p53 signaling pathway
Objective To explore the therapeutic effect of curcumol on hepatic fibrosis and its possible mechanism.Methods Human hepatic stellate cell line HSC-LX2 was cultured with curcumol in different concentrations of 5,10,15,20,30,45,60,80 and 100 μmol/L for 24 hours.The cell viability was detected by CCK-8 method.Three concentrations of curcumol(10,20 and 30 μmol/L)were selected for subsequent experiments.The expressions of α-smooth muscle actin(α-SMA),α1(Ⅰ)collagen and fibronectin were detected by Western blot and immunofluorescence assay.Senescent cells were detected by senescence-associated β-galactosidase(SA-β-Gal)staining.The mRNA expressions of senescence markers p1 6,p21,high mobility group protein A1(HMGA1)and telomerase reverse transcriptase(TERT)were detected by real-time quantitative PCR Western blot was used to detect the protein expressions of silencing mating type information regulator 2 homolog 1(Sirt1)and p53.Results Compared with curcumol 0 μmol/L,curcumol 20 and 30 μmol/L downregulated the expressions of α-SMA,α1(Ⅰ)collagen and fibronectin,increased SA-β-Gal staining positive cells,mRNA expressions of p16,p21 and HMGA1 and protein expression of p53,decreased TERT mRNA expression and Sirt1 protein expression(P<0.05 or P<0.01).The mRNA expressions of p16 and p21 were decreased after adding Sirt1 agonist SRT 1720 5 μmol/L(P<0.01).Conclusion Curcumol could induce hepatic stellate cell senescence through Sirt1-p53 signaling pathway,thereby alleviating hepatic fibrosis.

CurcumolHepatic stellate cellCell senescenceHepatic fibrosisSilencing mating type information regulator 2 homolog 1-p53 signaling pathway

金春、吴逢婧、冯丁丁、周杰

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210029 江苏南京,江苏卫生健康职业学院药学院

莪术醇 肝星状细胞 细胞衰老 肝纤维化 沉默交配型信息调节因子2同源蛋白1-p53信号通路

江苏卫生健康职业学院院级科研项目

JKD2021002

2024

江苏医药
江苏省人民医院(南京医科大学第一附属医院)

江苏医药

影响因子:0.707
ISSN:0253-3685
年,卷(期):2024.50(2)
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