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牛磺酸对体外肝星状细胞增殖和凋亡的影响。

Effects of taurine on proliferation and apoptosis of hepatic stellate cells in vitro.

作者信息

Chen Yue-Xiang, Zhang Xing-Rong, Xie Wei-Fen, Li Shi

机构信息

Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.

出版信息

Hepatobiliary Pancreat Dis Int. 2004 Feb;3(1):106-9.

Abstract

BACKGROUND

Hepatic fibrosis, a common response to chronic liver injury, is characterized by increased production of extracellular matrix components, whose major part is produced by hepatic stellate cells (HSCs). Taurine is a sulfur containing beta-amino acid rich in human body, and our previous experiments showed that it can inhibit the deposition of the extracellular matrix in the damaged liver. This work was to investigate the effects of taurine on proliferation and apoptosis of HSC and its possible mechanism.

METHODS

Cell proliferation was detected by the thiazole blue (MTT) colorimetric assay. Cell apoptosis and cell cycle were assessed via flow cytometry. The morphology of apoptotic cells was observed by phase-contrast fluorescent micrography after orange acridine staining, and the cAMP content was measured by radioimmunoassay. The expression of c-jun and c-fos was determined by the combination of immunocytochemistry and image analysis software.

RESULTS

Taurine dose-dependently inhibited the proliferation of HSCs at the concentration of 5-50 mmol/L, resulting in more cells in the G0/G1 phase and fewer in the S phase. Taurine markedly increased the synthesis of cAMP and suppressed the gene expression of c-jun and c-fos (P<0.01) in addition to the inhibition of the proliferative effect of platelet-derived growth factor BB on HSC. However, taurine had no effect on induction of cell apoptosis.

CONCLUSIONS

Taurine can significantly inhibit the proliferation of HSC, causing a G0/G1-phase arrest. This effect on HSC proliferation is associated with the enhancement of the synthesis of cAMP and inhibition of the gene expression of c-jun and c-fos. However it can not induce the apoptosis of HSC.

摘要

背景

肝纤维化是对慢性肝损伤的常见反应,其特征是细胞外基质成分产生增加,其中大部分由肝星状细胞(HSCs)产生。牛磺酸是人体内富含的一种含硫β-氨基酸,我们之前的实验表明它可以抑制受损肝脏中细胞外基质的沉积。本研究旨在探讨牛磺酸对肝星状细胞增殖和凋亡的影响及其可能机制。

方法

采用噻唑蓝(MTT)比色法检测细胞增殖。通过流式细胞术评估细胞凋亡和细胞周期。吖啶橙染色后用相差荧光显微镜观察凋亡细胞的形态,并用放射免疫分析法测定cAMP含量。采用免疫细胞化学和图像分析软件相结合的方法测定c-jun和c-fos的表达。

结果

在5-50 mmol/L浓度下,牛磺酸剂量依赖性地抑制肝星状细胞的增殖,导致更多细胞处于G0/G1期,S期细胞减少。除抑制血小板衍生生长因子BB对肝星状细胞的增殖作用外,牛磺酸还显著增加cAMP的合成并抑制c-jun和c-fos的基因表达(P<0.01)。然而,牛磺酸对诱导细胞凋亡没有作用。

结论

牛磺酸可显著抑制肝星状细胞的增殖,导致G0/G1期阻滞。这种对肝星状细胞增殖的作用与cAMP合成的增强以及c-jun和c-fos基因表达的抑制有关。然而,它不能诱导肝星状细胞凋亡。

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