中国组织工程研究 ›› 2012, Vol. 16 ›› Issue (19): 3427-3432.doi: 10.3969/j.issn.1673-8225.2012.19.002

• 骨髓干细胞 bone marrow stem cells • 上一篇    下一篇

骨髓间充质干细胞调控尿激酶型纤溶酶原激活物表达及其对大鼠肝星状细胞凋亡的影响**★

宁  琳,姜海行,覃山羽,张君红,杨  文,孟云超   

  1. 广西医科大学第一附属医院消化内科,广西壮族自治区南宁市530021
  • 收稿日期:2012-02-09 修回日期:2012-03-09 出版日期:2012-05-06 发布日期:2012-05-06
  • 通讯作者: 姜海行,博士,教授,博士生导师,广西医科大学第一附属医院消化内科,广西壮族自治区南宁市 530021 jihaxi@163.com
  • 作者简介:宁琳★,女,广西壮族自治区钦州市人,壮族,广西医科大学在读硕士,主要从事干细胞及干星状细胞凋亡机制研究。1223163675@qq.com
  • 基金资助:

    广西自然科学基金资助项目(0897008),广西“新世纪十百千人才工程”专项基金资助项目(2006206)。

Bone marrow mesenchymal stem cells increased expression of urokinase type plasminogen activator and promoted apoptosis of hepatic stellate cells in rats   

Ning Lin, Jiang Hai-xing, Qin Shan-yu, Zhang Jun-hong, Yang Wen, Meng Yun-chao   

  1. Department of Digestive Medicine, First Affiliated Hospital of Guangxi Medical University, Nanning  530021, Guangxi Zhuang Autonomous Region, China
  • Received:2012-02-09 Revised:2012-03-09 Online:2012-05-06 Published:2012-05-06
  • Contact: Jiang Hai-xing, M.D., Professor, Doctoral supervisor, Department of Digestive Medicine, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China jihaxi@163.com
  • About author:Ning Lin★, Studying for master’s degree, Department of Digestive Medicine, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China 1223163675@qq.com
  • Supported by:

    the Natural Science Foundation of Guangxi Zhuang Autonomous Region, No. 0897008*; the New Centuary National Hundred, Thousand and Ten Thousand Talent Project, No. 2006206*

摘要:

背景:骨髓间充质干细胞主要通过旁分泌及激活肝细胞生长因子促进肝星状细胞凋亡。
目的:观察骨髓间充质干细胞对尿激酶型纤溶酶原激活物合成的调控及肝细胞生长因子活性的影响,探讨其诱导肝星状细胞凋亡的机制。
方法:实验分为5组:①共培养组:大鼠骨髓间充质干细胞与肝星状细胞建立上下双层细胞共培养体系。②肝星状细胞单独培养组。③纤维原细胞对照组。④UK122干预组:在骨髓间充质干细胞与肝星状细胞共培养6 h前加入尿激酶型纤溶酶原激活物特异性抑制剂UK122。⑤骨髓间充质干细胞空白对照组。
结果与结论:共培养组尿激酶型纤溶酶原激活物mRNA表达较肝星状细胞单独培养明显增加(P < 0.01)。与肝星状细胞单独培养相比,共培养组的肝星状细胞在与骨髓间充质干细胞共培养24 h后表现明显增殖抑制(P < 0.01),且呈现时间依赖性;骨髓间充质干细胞与肝星状细胞共培养后,活性肝细胞生长因子的蛋白表达及肝星状细胞凋亡增加(P < 0.01)。UK122干预后活性肝细胞生长因子表达及肝星状细胞凋亡减少(P < 0.01)。提示骨髓间充质干细胞通过促进分泌尿激酶型纤溶酶原激活物,增加活性肝细胞生长因子表达,促进肝星状细胞凋亡。

关键词: 肝星状细胞, 骨髓间充质干细胞, 凋亡, 肝细胞生长因子, 尿激酶型纤溶酶原激活物

Abstract:

BACKGROUND: Bone marrow mesenchymal stem cells (BMSCs) promote the apoptosis of hepatic stellate cells (HSCs) by paracrine and activation of hepatocyte growth factor (HGF). 
OBJECTIVE: To investigate the effects of BMSC regulation to urokinase type plasminogen activator on activity of hepatocyte growth factor, and the mechanism by which BMSCs induce the apoptosis of hepatic stellate cells.
METHODS: Five groups were divided randomly: Co-culture group, in which rat BMSCs and HSCs were co-cultured by upper and down double-layer co-culture system; HSCs group, in which HSCs were simply cultured; fibroblasts group; UK122 pretreated group: 6 hours before co-culture of BMSCs and HSCs, urokinase type plasminogen activator specific inhibitor UK122 was added; BMSCs blank control group.
RESULTS AND CONCLUSION: mRNA expression of urokinase type plasminogen activator in the co-culture group was significantly higher than in the HSCs group (P < 0.01). Compared with HSC group, HSC proliferation was significantly inhibited in the co-culture group at 24 hours (P < 0.01) in a time-dependent manner. After co-culture, HGF protein expression and HSC apoptosis were significantly increased (P < 0.01). After UK122 intervention, HGF expression and HSC apoptosis were significantly decreased (P < 0.01). These findings suggest that BMSCs promote the secretion of urokinase type plasminogen activator, increase the expression of active HGF, and promote the apoptosis of HSCs.

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