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过氧化物酶体增殖物激活受体 γ 激动剂可减少系统性硬化症成纤维细胞的增殖和活力,并增加其凋亡。

Peroxisome proliferator-activated receptor γ agonists reduce cell proliferation and viability and increase apoptosis in systemic sclerosis fibroblasts.

机构信息

Department of Internal Medicine, Metabolism Unit, University of Pisa School of Medicine, Via Roma 67, I-56100 Pisa, Italy.

出版信息

Br J Dermatol. 2013 Jan;168(1):129-35. doi: 10.1111/j.1365-2133.2012.11199.x. Epub 2012 Oct 5.

Abstract

BACKGROUND

No study has evaluated the effect of the peroxisome proliferator-activated receptor γ (PPARγ) agonists on cell viability, proliferation and apoptosis in cultured systemic sclerosis (SSc) fibroblasts.

OBJECTIVES

The effects of two pure PPARγ agonists (rosiglitazone and pioglitazone) in cultured SSc fibroblasts were evaluated and compared with effects in normal fibroblasts.

METHODS

The study included evaluation of cell viability and proliferation (based on the cleavage of tetrazolium salts and measurement of absorbance of the cell proliferation reagent WST-1), and determination of cell apoptosis (by means of the Hoechst dye uptake).

RESULTS

Rosiglitazone or pioglitazone (20μmolL(-1) ) significantly reduced cell proliferation (cell count of 75% and 83% compared with baseline, respectively, after 2h) and cell viability (absorbance reductions of 25% and 22% compared with baseline, respectively, after 2 h), and increased apoptosis (apoptotic cell percentages 9·9% and 8·6%, respectively, after 48h of incubation) in SSc fibroblasts, whereas they did not present a significant influence on control fibroblasts.

CONCLUSIONS

The effects of rosiglitazone or pioglitazone shown on SSc fibroblasts raise the hypothesis of a therapeutic role for PPARγ agonists in patients affected by SSc.

摘要

背景

目前尚无研究评估过过氧化物酶体增殖物激活受体γ(PPARγ)激动剂对培养的系统性硬化症(SSc)成纤维细胞活力、增殖和凋亡的影响。

目的

评估两种纯 PPARγ 激动剂(罗格列酮和吡格列酮)对培养的 SSc 成纤维细胞的作用,并与正常成纤维细胞的作用进行比较。

方法

本研究包括评估细胞活力和增殖(基于四唑盐的裂解和细胞增殖试剂 WST-1 的吸光度测量),以及测定细胞凋亡(通过 Hoechst 染料摄取)。

结果

罗格列酮或吡格列酮(20μmolL(-1))可显著降低 SSc 成纤维细胞的增殖(与基线相比,培养 2 小时后细胞计数分别减少 75%和 83%)和活力(与基线相比,培养 2 小时后吸光度分别降低 25%和 22%),并增加细胞凋亡(培养 48 小时后凋亡细胞百分比分别为 9.9%和 8.6%),而对对照成纤维细胞则没有明显影响。

结论

罗格列酮或吡格列酮对 SSc 成纤维细胞的作用提示 PPARγ 激动剂在 SSc 患者中可能具有治疗作用。

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