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蛇床子素对增生性瘢痕成纤维细胞凋亡及转化生长因子-β1的影响

Effects of osthole on apoptosis and TGF-beta1 of hypertrophic scar fibroblasts.

作者信息

Hou Xiao-Hua, Cao Bo, Liu Hong-Qi, Wang Yi-Zheng, Bai Shu-Fang, Chen Hong

机构信息

Affiliated Hospital of Medical College of Chinese People's Armed Police Forces, Tianjin, China.

出版信息

J Asian Nat Prod Res. 2009 Jul;11(7):663-9. doi: 10.1080/10286020902975772.

DOI:10.1080/10286020902975772
PMID:20183304
Abstract

Osthole, 7-methoxy-8-[3-methylpent-2-enyl]coumarin (1), was extracted from a Chinese herb Cnidium monnieri (L.) Cuss. It showed immunity strengthening, anti-tumor, anti-hepatitis, and anti-osteoporosis activities in previous studies. Our goals are to study the effects of 1 on cell proliferation and TGF-beta of hypertrophic scar fibroblasts. Our results showed that 1 induced apoptosis and inhibited cell proliferation in hypertrophic scar fibroblasts. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that its IC(50) value toward hypertrophic scar fibroblasts was 15.5 +/- 2.2 micromol/l. Furthermore, the results of cell growth curve matched with the above results. Inducing apoptosis by 1 in hypertrophic scar fibroblasts was assessed by various morphological and biochemical characteristics, including cell shrinkage, chromatin condensation, membrane blebbing, formation of apoptotic bodies, and DNA ladder formation. A typical 'Sub-G(1) peak' was also checked through flow cytometry. We used immunohistochemistry to observe the expression of TGF-beta(1). Also, we found that 1 could obviously inhibit the expression of TGF-beta(1) of fibroblasts derived from hypertrophic scar compared with the control group (P < 0.05). These results suggest that 1 inhibits the growth of hypertrophic scar fibroblasts through apoptosis and decreases the expression of TGF-beta(1).

摘要

蛇床子素,即7-甲氧基-8-[3-甲基戊-2-烯基]香豆素(1),是从一种中药材蛇床(Cnidium monnieri (L.) Cuss.)中提取出来的。在先前的研究中,它显示出增强免疫力、抗肿瘤、抗肝炎和抗骨质疏松的活性。我们的目标是研究1对增生性瘢痕成纤维细胞的细胞增殖和转化生长因子-β(TGF-β)的影响。我们的结果表明,1诱导增生性瘢痕成纤维细胞凋亡并抑制其细胞增殖。3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)检测显示,其对增生性瘢痕成纤维细胞的半数抑制浓度(IC50)值为15.5±2.2微摩尔/升。此外,细胞生长曲线的结果与上述结果相符。通过各种形态学和生化特征评估1诱导增生性瘢痕成纤维细胞凋亡的情况,包括细胞皱缩、染色质凝聚、细胞膜起泡、凋亡小体形成以及DNA梯状条带形成。还通过流式细胞术检测到了典型的“亚G1峰”。我们使用免疫组织化学观察TGF-β1的表达。并且,我们发现与对照组相比,1能明显抑制增生性瘢痕来源的成纤维细胞中TGF-β1的表达(P<0.05)。这些结果表明,1通过诱导凋亡抑制增生性瘢痕成纤维细胞的生长,并降低TGF-β1的表达。

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