|本期目录/Table of Contents|

[1]张丽,方步武.虎杖苷抑制肝星状细胞增殖活化的作用和机制研究[J].天津医科大学学报,2020,26(04):309-312.
 ZHANG Li,FANG Bu-wu.Inhibitory effects and mechanism of Polydatin on the proliferation and activation of hepatic stellate cell[J].Journal of Tianjin Medical University,2020,26(04):309-312.
点击复制

虎杖苷抑制肝星状细胞增殖活化的作用和机制研究(PDF)
分享到:

《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:
26卷
期数:
2020年04期
页码:
309-312
栏目:
基础医学
出版日期:
2020-07-15

文章信息/Info

Title:
Inhibitory effects and mechanism of Polydatin on the proliferation and activation of hepatic stellate cell
文章编号:
1006-8147(2020)04-0309-04
作者:
张丽方步武
(天津医科大学基础医学院药理学系,天津300070)
Author(s):
ZHANG Li FANG Bu-wu
(Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China)
关键词:
虎杖苷肝纤维化肝星状细胞Nrf2HO-1
Keywords:
Polydatin hepatic fibrosis hepatic stellate cell Nrf2 HO-1
分类号:
R96
DOI:
-
文献标志码:
A
摘要:
目的:研究虎杖苷 (Polydatin) 在体外对HSC-T6细胞的影响,探讨虎杖苷抑制肝纤维化发生的作用及相关机制。方法:体外培养大鼠肝星状细胞HSC-T6,分为对照组和虎杖苷低、中、高浓度(125、250、500 μmol/L)给药组。MTT法检测细胞增殖情况;比色法检测细胞培养上清液中乳酸脱氢酶(LDH)的活性;酶消化法检测细胞培养上清液中羟脯氨酸(Hyp)的含量;蛋白印迹法检测α-平滑肌肌动蛋白(α-SMA)、Ⅰ型胶原(CollagenⅠ)、核因子NF-E2相关因子2(Nrf2)和血红素加氧酶-1(HO-1)蛋白表达水平。多组间比较采用单因素方差分析,若方差齐则采用LSD检验,若方差不齐采用Dunnett T3检验,以P<0.05认为差异有统计学意义。结果:与对照组比较,虎杖苷125、250、500 μmol/L给药组细胞活力显著降低(F=252.01, P<0.001),Hyp含量明显减少(F=16.50,P<0.05),α-SMA和CollagenⅠ蛋白表达显著减少(F=19.89、182.91, 均P<0.05),且随着浓度的增加,抑制作用越强,呈一定的剂量依赖性;与对照组比较,虎杖苷125、250、500 μmol/L给药组Nrf2蛋白表达显著增加(F=23.70,P<0.05),虎杖苷250、500 μmol/L给药组HO-1蛋白表达显著增加(F=12.40,P<0.01),且随着浓度增加,上调作用越明显,呈一定的剂量依赖性。结论:虎杖苷通过抑制肝星状细胞增殖活化及胶原合成发挥抑制肝纤维化发生的作用,该作用可能与其上调Nrf2/HO-1通路有关。
Abstract:
Objective: To examine the effect of Polydatin on HSC-T6 cells in vitro, and to investigate the inhibitory effects and related mechanism of Polydatin on liver fibrogenesis. Methods: Rat hepatic stellate cells HSC-T6 were cultured in vitro and were divided into control group and low, middle and high concentration(125, 250, 500 μmol/L)Polydatin groups. Cell proliferation was measured by MTT assay. LDH activity in cell supernatant was detected by colorimetryassay. Hypcontentin cell supernatant was examined by enzyme digestion assay.Protein expression levels of α-SMA(Alpha-smooth muscle actin), CollagenⅠ,Nrf2(NF-E2-related factor 2) and HO-1 (heme oxygenase-1) were detected by Western blot. One-Way ANOVA was used for comparison among multiple groups. If the variances were homogeneous, LSD test was used; if the variances were heterogeneous, Dunnett T3 test was used. A value of P<0.05 was considered different significantly. Results: Compared with the control group, for the Polydatin 125, 250, 500 μmol/L groups, the cell viability was significantly reduced(F=252.01, P<0.001), the Hyp content was significantly reduced(F=16.50, P<0.05), the protein expression of α-SMA and CollagenⅠwere decreased significantly(F=19.89, 182.91, all P<0.05). And with the increase of the concentration, the inhibitory effect was stronger and in a certain dose-dependent manner. Compared with control group, the protein expression of Nrf2 was increased significantly in Polydatin125, 250, 500 μmol/L groups (F=23.70, P<0.05) and the protein expression of HO-1 was increased significantly in Polydatin 250, 500 μmol/L groups(F=12.40, P<0.01), and with the increase of the concentration, the upregulative effect was stronger and in a certain dose-dependent manner. Conclusion:Polydatin can inhibit hepatic fibrogenesis by inhibiting the collagen synthesis and proliferation and activation of hepatic stellate cells, which may be associated with the upregulation of Nrf2/HO-1 pathway.

参考文献/References:

[1] Aydm M M, Akcahal K C. Liver fibrosis[J]. Turk J Gastroenterol, 2018, 29(1): 14
[2] Hu D, Hu Y, Xu W, et al. miR-203 inhibits the expression of collagen-related genes and the proliferation of hepatic stellate cells through a SMAD3-dependent mechanism[J]. Mol Med Rep, 2017, 16(2): 1248
[3] Fujiki T, Ando F, Murakami K, et al. Tolvaptan activates the Nrf2/HO-1 antioxidant pathway through PERK phosphorylation[J]. Sci Rep, 2019, 9(1): 9245
[4] Suzuki T, Yamamoto M. Stress-sensing mechanisms and the physiological roles of the Keap1-Nrf2 system during cellular stress[J]. J Biol Chem, 2017, 292(41): 16817
[5] Jiao Y, Wu Y, Du D. Polydatin inhibits cell proliferation, invasion and migration, and induces cell apoptosis in hepatocellular carcinoma[J]. Braz J Med BiolRes, 2018, 51(4): e6867
[6] Du Q H, Peng C, Zhang H. Polydatin: a review of pharmacology and pharmacokinetics[J]. Pharm Biol, 2013, 51(11): 1347
[7] Zhang D Y, Friedman S L. Fibrosis-dependent mechanisms of hepatocarcinogenesis[J]. Hepatology, 2012, 56(2): 769
[8] Ezhilarasan D, Sokal E, Najimi M. Hepatic fibrosis: it is time to go with hepatic stellate cell-specific therapeutic targets[J]. Hepatobiliary Pancreat Dis Int, 2018, 17(3): 192
[9] Tsuchida T, Friedman S L. Mechanisms of hepatic stellate cell activation[J]. Nat Rev Gastroenterol Hepatol, 2017, 14(7): 397
[10] Li P, Wu G. Roles of dietary glycine, proline, and hydroxyproline in collagen synthesis and animal growth[J]. Amino Acids, 2018, 50(1): 29
[11] Cai Z, Lou Q, Wang F, et al. N-acetylcysteine protects against liver injure induced by carbon tetrachloride via activation of the Nrf2/HO-1 pathway[J]. Int J Clin Exp Pathol, 2015, 8(7):8655
[12] Zhang G, Cui R, Kang Y, et al. Testosterone propionate activated the Nrf2-ARE pathway in ageing rats and ameliorated the age-related changes in liver[J]. Sci Rep, 2019, 9(1): 18619
[13] Yang H, Chen B, Zhao Z, et al. Heme oxygenase-1 exerts pro-apoptotic effects on hepatic stellate cells in vitro through regulation of nuclear factor-κB[J]. Exp Ther Med, 2018, 16(1): 291
[14] Jiang J, Chen Y, Dong T, et al. Polydatin inhibits hepatocellular carcinoma via the AKT/STAT3-FOXO1 signaling pathway[J]. Oncol Lett, 2019, 17(5): 4505
[15] Lai Y, Zhou C, Huang P, et al. Polydatin alleviated alcoholic liver injury in zebrafish larvae through ameliorating lipid metabolism and oxidative stress[J]. J Pharmacol Sci, 2018, 138(1): 46
[16] Xu L Q, Xie Y L, Gui S H, et al. Polydatin attenuates d-galactose-induced liver and brain damage through its anti-oxidative, anti-inflammatory and anti-apoptotic effects in mice[J]. Food Funct, 2016, 7(11): 4545
[17] Liu Y H, Huang Q H, Wu X, et al. Polydatin protects against acetaminophen-induced hepatotoxicity in mice via anti-oxidative and anti-apoptotic activities[J]. Food Funct, 2018, 9(11): 5891

相似文献/References:

[1]刘文东,李英娴,娄婷婷,等.青蒿琥酯对肝纤维化大鼠肝组织基质金属蛋白酶表达的影响[J].天津医科大学学报,2013,19(05):362.
[2]徐亚洁,张晓燕,马淑晶,等.神经酰胺对肝纤维化治疗作用的初步研究[J].天津医科大学学报,2014,20(04):260.
 XU Ya-jie,ZHANG Xiao-yan,MA Shu-jing,et al.Effects of ceramide on hepatic fibrosis[J].Journal of Tianjin Medical University,2014,20(04):260.
[3]张晓燕,马淑晶,徐亚洁,等.青蒿琥酯对人源肝星状细胞LX-2增殖、胶原产生以及KLF6表达的影响[J].天津医科大学学报,2014,20(04):257.
 ZHANG Xiao-yan,MA Shu-jing,XU Ya-jie,et al.Effects of artesunate on cell proliferation,collagen generated and KLF6 expression in hepatic stellate cells[J].Journal of Tianjin Medical University,2014,20(04):257.
[4]李萌乾,王青松,郭正隆,等.诱导型狨猴肝纤维化模型的建立 [J].天津医科大学学报,2014,20(06):433.
 LI Meng-qian,WANG Qing-song,GUO Zheng-long,et al. Establishment of drug-induced common marmoset model for hepatic fibrosis[J].Journal of Tianjin Medical University,2014,20(04):433.
[5]刘 悦,李杉杉,唐诗慧,等.蒿鳖养阴软坚方通过激活Nrf2/NQO1信号通路抑制肝纤维化发生[J].天津医科大学学报,2018,24(01):19.
 LIU Yue,LI Shan-shan,TANG Shi-hui,et al.Effects of HaobieYangyinRuanjian on inhibition of hepatic fibroesis through upregulated Nrf2/NQO1 pathway[J].Journal of Tianjin Medical University,2018,24(04):19.
[6]卢娜,方步武.蒿鳖养阴软坚方对刀豆球蛋白A诱导的肝纤维化Nrf2/HO-1信号通路影响[J].天津医科大学学报,2018,24(02):112.
 LU Na,FANG Bu-wu.Effect of Haobie yangyin ruanjian prescription on Nrf2/HO-1 signaling pathway in ConA-induced hepatic fibrosis[J].Journal of Tianjin Medical University,2018,24(04):112.
[7]靳悦,汪河,李明威,等.CD24 通过调节肝内Ly6Clo 巨噬细胞亚群中PDGF-B 的 分泌抑制肝纤维化进程[J].天津医科大学学报,2022,28(03):260.
 JIN Yue,WANG He,LI Ming-wei,et al.CD24 inhibits the liver fibrosis process by regulating the secretion of PDGF -B in hepatic Ly6Clo macrophage subset[J].Journal of Tianjin Medical University,2022,28(04):260.
[8]刘志杰综述,詹江华审校.肝巨噬细胞在胆道闭锁肝纤维化中的作用[J].天津医科大学学报,2023,29(04):453.
[9]翁飞鸿,周一平,伊思敏,等.肝纤维化的病理学发生机制及诊疗研究进展[J].天津医科大学学报,2023,29(05):559.

备注/Memo

备注/Memo:
作者简介 张丽(1995-),女,硕士在读,研究方向:中药药理学;
通信作者:方步武,E-mail:fangdch@aliyun.com.cn。
更新日期/Last Update: 2020-07-15