[1]孔德松,张自力,张 峰,等.姜黄素通过影响自噬调控肝细胞上皮间质转化及肝纤维化进程的作用与机制研究[J].中国药理学通报,2019,(10):1388-1393.[doi:10.3969/j.issn.1001-1978.2019.10.012]
 KONG De-song,ZHANG Zi-li,ZHANG Feng,et al.Curcumin blunt epithelial to mesenchymal transduction of hepatocytes to aggravate liver fibrosis through promoting autophagy in hepatocytes[J].Chinese Pharmacological Bulletin,2019,(10):1388-1393.[doi:10.3969/j.issn.1001-1978.2019.10.012]
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姜黄素通过影响自噬调控肝细胞上皮间质转化及肝纤维化进程的作用与机制研究()
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《中国药理学通报》[ISSN:/CN:]

卷:
期数:
2019年10期
页码:
1388-1393
栏目:
论著
出版日期:
2019-09-15

文章信息/Info

Title:
Curcumin blunt epithelial to mesenchymal transduction of hepatocytes to aggravate liver fibrosis through promoting autophagy in hepatocytes
文章编号:
1001-1978(2019)10-1388-06
作者:
孔德松1张自力23张 峰23郑仕中23
1.南京中医药大学附属南京中医院科研部,江苏 南京 210001; 2.南京中医药大学 药学院药理学教研室,江苏 南京 210023; 3.江苏省中药药效与安全性评价重点实验室,江苏 南京 210023
Author(s):
KONG De-song1 ZHANG Zi-li2 3 ZHANG Feng2 3 ZHENG Shi-zhong2 3
1.Scientific Research Dept, Nanjing Hospital of Chinese Medicine, Nanjing University of Chinese Medicine,Nanjing 210001, China; 2.Pharmacology Dept, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; 3.Jiangsu Key Labfor Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China
关键词:
姜黄素 肝纤维化 上皮间质转化 自噬 肝细胞 肌成纤维细胞
Keywords:
curcumin liver fibrosis epithelial-mesenchymal transition autophagy hepatocyte myofibroblast
分类号:
R-332; R282.71; R322.47; R329.24; R575.2
DOI:
10.3969/j.issn.1001-1978.2019.10.012
文献标志码:
A
摘要:
目的 明确自噬在姜黄素调控肝细胞上皮间质转化进程及向肌成纤维细胞转变中的作用,阐明其中的调控机制。方法 小鼠胚胎肝细胞BNL CL.2,与构建的BECN1基因干扰BNL CL.2细胞,以TGF-β1(2 μg·L-1)处理细胞,给予姜黄素(10、20、30 μmol·L-1)干预,real-time PCR与Western blot检测BNL CL.2细胞Beclin-1、LC3、Vimentin及α-SMA基因与蛋白的表达情况,光学显微镜下观察细胞形态变化,GFP-LC3质粒转染监测细胞自噬水平变化。结果 TGF-β1处理后,自噬水平下降,BNL CL.2细胞Vimentin及α-SMA表达增加,细胞形态发生间质型转变。姜黄素能抑制TGF-β1诱导后肝细胞Vimentin及α-SMA的表达,增加肝细胞自噬相关基因与蛋白BECN1、LC3的表达,升高细胞自噬水平,抑制肝细胞的上皮间质转化进程。干扰自噬相关基因BECN1后,姜黄素抑制肝细胞上皮间质转化的效应被部分阻断。结论 姜黄素通过提高肝细胞自噬水平,抑制肝细胞上皮间质转化进程,进而抑制肝纤维化的发生与发展。
Abstract:
Aim To clarify the role of autophagy in the regulation mechanism of epithelial-mesenchymal transition(EMT)in hepatocytes and the transition to myofi-broblast.Methods BNL CL.2, a mouse embryonic hepatocyte, and BNL CL.2 cells knocked-down BECN1 genes were treated with TGF-β1(2 μg·L-1)and curcumin(10, 20, 30 μmol·L-1).Real-time PCR and Western blot were used to detect Beclin-1, LC3, Vimentin and α-SMA gene and protein expression in BNL cl.2 cells.The optical microscope was used to observe the changes of cell morphology.And the changes in cell autophagy were detected by GFP-LC3 plasmid transfection.Results After the intervention of TGF-β1, the expression of Vimentin and α-SMA, the mesenchymal marker, increased and the autophagy decreased.Curcumin could inhibit Vimentin and α-SMA expression in hepatocytes.Moreover, curcumin could increase the autophagy related genes and protein expression of Beclin-1 and LC3 in hepatocytes.Curcumin could increase the level of autophagy and inhibit the cell transformation to myofibroblast-like cells.After interfering with BECN1, the effect of curcumin inhibiting hepatic EMT was partially blocked.Conclusions Curcumin could inhibit the process of EMT of hepatocytes by increasing the level of autophagy.The occurrence and development of liver fibrosis was consequently inhibited.

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备注/Memo

备注/Memo:
收稿日期:2019-07-20,修回日期:2019-08-16 基金项目:国家自然科学基金资助项目(No 81600483); 中国肝炎防治基金会天晴肝病研究基金项目(No TQGB20170027); 江苏省“六大人才”高峰项目; 南京市医学科技发展项目(No YKK17153) 作者简介:孔德松(1989-),男,硕士,助理研究员,研究方向:天然药物预防和治疗肝纤维化与肿瘤,Tel:025-52276505,E-mail:kongds0675@126.com; 郑仕中(1962-),男,博士,教授,博士生导师,研究方向:天然药物预防和治疗肝纤维化与肿瘤,通讯作者,Tel:025-85811246,E-mail:nytws@163.com
更新日期/Last Update: 2019-09-15