An anti-fibrosis mechanism study on effects of difference in iron load levels on activation and apoptosis of hepatic stellate cells
10.3969/j.issn.1008-9691.2013.05.013
- VernacularTitle:不同铁负载水平影响肝星状细胞活化和凋亡的抗肝纤维化机制研究
- Author:
Yuan JIANG
;
Ling ZHANG
;
Yuanqi DENG
;
Jinyang HE
- Publication Type:Journal Article
- Keywords:
Hepatic stellate cell;
Liver fibrosis;
Iron;
Desferrioxamine;
Activation;
Apoptosis
- From:
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care
2013;(6):369-373
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the anti-fibrosis mechanism from effects of difference in iron load levels on activation and apoptosis of hepatic stellate cells(HSCs). Methods According to the difference in iron load levels in HSCs,HSC-T6 cells were divided into four groups:blank control,iron deposition model,50μmol/L desferrioxamine and 25 μmol/L desferrioxamine groups. Quantitative polymerase chain reaction(PCR)was applied for the detection of collagen type Ⅰ and transforming growth factor-β1(TGF-β1)mRNA expressions of HSC-T6 cells. Immunohistochemical assay was used for the detection of α-smooth muscle actin(α-SMA)expression. The method of terminal deoxynucleotidyl transferase(TdT)-mediated dUTP nick end labeling(TUNEL)was used for the examination of apoptosis of HSC-T6 cells. Under electron microscope,the ultrastructures of HSC-T6 cells were observed. Results Compared with the blank control group,despite the TGF-β1 mRNA expression in iron deposition model group was increased,no statistical significant difference was seen(1.594±0.168 vs. 1.477±0.126, P>0.05),whereas collagen type I mRNA expression was significantly enhanced(1.354±0.076 vs. 1.197±0.104, P<0.01). Both 50μmol/L and 25μmol/L desferrioxamine could down-regulate collagen type I and TGF-β1 mRNA expressions,and the action of 50μmol/L desferrioxamine was superior to that of 25μmol/L desferrioxamine(collagen typeⅠmRNA:0.391±0.076 vs. 0.688±0.060,TGF-β1 mRNA:0.421±0.068 vs. 0.714±0.090,both P<0.01). Iron deposition could induce HSCs to expressα-SMA in great amount,while apoptosis could be seen scarcely in iron deposited HSCs. By desferrioxamine therapy,α-SMA expression of HSCs was decreased significantly,but some of the cells underwent apoptosis. Conclusion Different iron load levels inside HSCs can induce activation or apoptosis of the cells,showing that iron plays an important role in regulating the process of HSCs activation and apoptosis and revealing that desferrioxamine possesses the potential action for treatment of liver fibrosis.
