中国组织工程研究 ›› 2011, Vol. 15 ›› Issue (10): 1736-1740.doi: 10.3969/j.issn.1673-8225.2011.10.006

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

硫化氢抑制顺铂致人骨髓间充质干细胞的损伤

李敬春1,2,黄  纲1,雍碧城1,徐名洪1,王姚斐1,张泷涓2   

  1. 中山大学附属第一医院,1骨肿瘤科,2外科实验室,广东省广州市510080
  • 收稿日期:2010-10-01 修回日期:2010-12-20 出版日期:2011-03-05 发布日期:2011-03-05
  • 通讯作者: 黄纲,博士,副教授,副主任医师,中山大学附属第一医院骨肿瘤科,广东省广州市 10080 ganghuang@163.net
  • 作者简介:李敬春★,男,1984年生,山东省枣庄市人,汉族,中山大学在读硕士,主要从事骨肉瘤基础研究。 jingchun999@yahoo.com.cn
  • 基金资助:

    广东省自然科学基金(07001667),课题名称:转移性骨肉瘤分子遗传学特征性研究。

Hydrogen sulfide protects human bone marrow mesesenchymal stem cells against cisplatin-induced damage

Li Jing-chun1, 2, Huang Gang1, Yong Bi-cheng1, Xu Ming-hong1, Wang Yao-fei1, Zhang Long-juan2   

  1. 1Department of Orthopedic-Oncology, 2Laboratory of Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou  510080, Guangdong Province, China
  • Received:2010-10-01 Revised:2010-12-20 Online:2011-03-05 Published:2011-03-05
  • Contact: Huang Gang, Doctor, Associate professor , Associate chief physician, Department of Orthopedic-Oncology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China ganghuang@163.net
  • About author:Li Jing-chun★, Studying for master’s degree, Department of Orthopedic- Oncology, Laboratory of Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China jingchun999@yahoo.com.cn
  • Supported by:

    Natural Science Foundation of Guangdong Province, No. 07001667*

摘要:

背景:在使用顺铂进行化疗时,常因造血干细胞损伤造成严重的骨髓抑制,而目前临床上还没有一种有效的化疗细胞保护剂来减轻其不良反应。
目的:探讨硫化氢对顺铂致人骨髓间充质干细胞损伤的保护作用。
方法:应用硫氢化钠作为硫化氢的供体,用不同浓度的硫氢化钠与顺铂同时作用于人骨髓间充质干细胞48 h后,甲氮甲唑蓝法(MTT)检测细胞存活率,Hoechst33258染色检测细胞凋亡,Western blot检测蛋白的表达。
结果与结论:MTT检测发现顺铂可降低骨髓间充质干细胞的存活率,硫氢化钠可呈浓度依赖性的对抗顺铂对人骨髓间充质干细胞生长的抑制作用,0.5,1 mmol/L 硫氢化钠与20 mg/L顺铂共同作用人骨髓间充质干细胞48 h后会引起NF-κB(p65)上调和IκB-α的下调,1 mmol/L 硫氢化钠与20 mg/L顺铂在作用6 h后磷酸化蛋白激酶1/2明显上调。结果提示,硫化氢可能通过蛋白激酶-NF-κB信号通路来抑制顺铂致人骨髓间充质干细胞的损伤作用。

关键词: 人骨髓间充质干细胞, 硫化氢, 细胞保护, 顺铂, 骨髓抑制

Abstract:

BACKGROUND: Due to serious myelosuppression caused by hemopoietic stem cell damage when using cisplatin chemo-treatment, there is no effective cytoprotective agent of chemo-treatment to lessen its adverse reaction.
OBJECTIVE: To explore the protection of hydrogen sulfide (H2S) against cisplatin–induced human bone marrow mesesenchymal stem cells (hBMSCs) damage.
METHODS: Sodium hydrosulfide (NaHS) as a H2S donor. hBMSCs treated with different concentrations of sodium hydrosulfide and cisplatin for 48 hours, the cell survival rate was measured by MTT assay; the morphological change of apoptotic cells was tested by using the chromatin dye Hoechst 33258; the proteins expression were detected with Western blot techniques.
RESULTS AND CONCLUSION: MTT detection showed that cisplatin chould reduce the survival rate of BMSCs, and NaHS dose-dependently blocked the inhibition of hBMSCs cells growth induced by cisplatin. When hBMSCs cells were treated by both NaHS (0.5, 1 mmol/L) and cisplatin (20 mg/L) for 48 hours, the NF-κB (p65) was up-regulated, but the IκB-α was down-regulated. When hBMSCs cells were treated by both NaHS (1 mmol/L) and cisplatin (20 mg/L) for 6 hours, the level of phosphorylated protein kinase 1/2 was significantly ascended. The results showed that H2S chould protect hBMSCs against cisplatin-induced damage, which may be associated with the activation of protein kinase-NF-κB signaling pathway.

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