骨髓间充质干细胞抑制皮肤瘢痕形成的机制研究
投稿时间:2015-09-21  修订日期:2015-10-30  点此下载全文
引用本文:武艳,杨岚,陈志会,李厚忠,王莹,袁晓环,金红.骨髓间充质干细胞抑制皮肤瘢痕形成的机制研究[J].医学研究杂志,2016,45(5):81-85
DOI: 10.11969/j.issn.1673-548X.2016.05.019
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作者单位E-mail
武艳 157011 牡丹江医学院医药研究中心  
杨岚 157011 牡丹江医学院红旗医院  
陈志会 157011 牡丹江医学院红旗医院  
李厚忠 157011 牡丹江医学院红旗医院 病理学教研室  
王莹 157011 牡丹江医学院红旗医院 解剖学教研室  
袁晓环 157011 牡丹江医学院医药研究中心  
金红 157011 牡丹江医学院红旗医院 jinhong198122@163.com 
基金项目:国家自然科学基金资助项目(81401599);黑龙江省自然科学基金资助项目(H201378);黑龙江省教育厅青年学术骨干支持计划项目(1254G064);黑龙江省普通本科高等学校青年创新人才培养计划(UNPYSCT-2015109)
中文摘要:目的 探讨骨髓间充质干细胞(BM-MSCs)抑制皮肤瘢痕形成的机制研究,为增生性瘢痕的防治提供实验基础。方法 C57BL/6小鼠随机分为空白对照组、移植对照组、模型组以及MSCs移植组(n=6)。对照组和移植对照组小鼠每日于背部经皮下注射1mlPBS,3h后移植对照组经皮下注射1×106个MSCs,对照组给予相同剂量的PBS,模型组和MSCs移植组小鼠每日于背部经皮下注射1ml(1mg/ml)博来霉素,3h后MSCs移植组经皮下注射1×106个MSCs,模型组给予相同剂量的PBS,共计3周。RT-PCR检测与瘢痕形成相关的基因表达,免疫组织化学法检测皮肤纤维化程度指标α-平滑肌肌动蛋白(α-SMA)的表达。结果 BM-MSCs下调了TGF-β1、Ⅰ型胶原及HSP47的表达,并且促进了MMP-2、MMP-9及MMP-13的表达,也使得α-SMA的表达下调。结论 MSCs可以重塑细胞外基质以及抑制肌成纤维细胞生成,从而抑制皮肤瘢痕形成,为MSCs在皮肤创伤修复领域中的应用提供了新的实验基础。
中文关键词:骨髓间充质干细胞  皮肤瘢痕  细胞外基质  成纤维细胞
 
Mechanism of Mesenchymal Stem Cells Inhibiting Skin Scar Development
Abstract:Objective To study the mechanism of BM-MSCs on inhibiting skin scar development, and to provide experimental basis for the prevention and treatment of hypertrophic scars. Methods Wild C57BL/6 mice (7-8 weeks old, female) were randomly divided into four groups (n=6, per group).In Control group, PBS was injected into the dorsal skin of mice by subcutaneous injection every day.In MSCs transplantation control group, PBS was injected into the dorsal skin of mice, 1×106 BM-MSCs suspended in 0.1ml PBS were injected into the lesion skin after 3h by subcutaneous injection every day.In skin scar model group, 1mg/ml bleomycin was injected into the dorsal skin of mice by subcutaneous injection every day,and the lesion skin after 3 h by subcutaneous injection every day.In MSCs-treated group, bleomycin was injected into the dorsal skin of mice, and 1×106 BM-MSCs suspended in 0.1ml PBS were injected into the lesion skin after 3h by subcutaneous injection every day. After 3 weeks, skin specimens were harvested. mRNA expression levels of TGF-β1, type Ⅰ collagen and HSP47, (MMPs)-2, -9 and -13 were measured by RT-PCR, and α-SMA positive cells was detected by immunohistochemistry. Results Lesional skin with BM-MSCs treatment exhibited a significant down-regulation of TGF-β1, type Ⅰ collagen and HSP47, with higher MMPs-2, -9 and -13. Further experiments showed that α-SMA positive cells, the most reliable marker of myofibroblasts, apparently decreased after BM-MSCs transplantation. Conclusion BM-MSCs can inhibit skin scar development by remodeling extracellular matrix and inhibiting the proliferation of myofibroblasts, which may provide new theoretical supports for the application of MSCs in the field of cutaneous repair.
keywords:Mesenchymal stem cells  Skin scar  ECM  Fibroblasts
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