骨髓间充质干细胞拮抗氧化型低密度脂蛋白
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国家自然科学基金项目(30971235)


Bone Marrow Mesenchymal Stem Cells Attenuate Endothelial Cell Apoptosis Induced by ox-LDL
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    摘要:

    目的 探讨骨髓间充质干细胞(MSC)对氧化型低密度脂蛋白(ox-LDL)诱导的人脐静脉内皮细胞(HUVEC)凋亡的影响及有关机制。方法 将对数生长期的HUVEC分成三组:对照组单纯培养HUVEC;ox-LDL组的HUVEC给予100 mg/L ox-LDL培养24 h;ox-LDL+MSC组使用细胞培养池共同培养HUVEC和MSC,并加入100 mg/L ox-LDL培养24 h。采用流式细胞术检测HUVEC的凋亡情况,采用ELISA检测细胞培养上清液中肿瘤坏死因子α(TNF-α)和血管内皮生长因子(VEGF)的含量,并通过Real-time PCR检测HUVEC中凋亡相关基因Bcl-2与Bax mRNA的表达情况。结果 在100 mg/L ox-LDL作用24 h后,细胞凋亡率明显上升,细胞培养上清液中TNF-α、VEGF含量明显上升,Bcl-2 mRNA表达下调,而Bax mRNA表达上调。MSC与HUVEC共培养可增加上清液中VEGF含量,减少TNF-α含量,上调Bcl-2 mRNA表达,下调Bax mRNA表达,使内皮细胞凋亡率明显下降。结论 MSC可以拮抗ox-LDL诱导的血管内皮细胞凋亡,可能与其分泌VEGF、抑制炎性反应并上调Bcl-2 mRNA表达及下调Bax mRNA表达有关,为MSC治疗动脉粥样硬化等内皮损伤性疾病进一步提供了理论基础。

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    Aim To investigate whether bone marrow mesenchymal stem cells (MSC) reduce the apoptosis of human umbilical vein endothelial cells (HUVEC) induced by oxidized low density lipoprotein (ox-LDL),and related mechanisms. Methods The HUVEC were divided into three groups: HUVEC were cultured in normol medium HUVEC were cultured with 100 mg/L ox-LDL for 24 h and HUVEC were cocultured with MSC with 100 mg/L ox-LDL for 24 h. Then cell apoptosis of different groups were mesured by flow cytometry. The content of VEGF,as well as TNF-α,in supernatant medium were determined by ELISA,and Real-time PCR was used to detect Bcl-2 and Bax mRNA expression. Results After 24 h stimulated by ox-LDL,the HUVEC apoptosis rate was increased,and the content of VEGF,TNF-α were significantly increased,while Bcl-2 mRNA expression was downregulated and Bax mRNA upregulated. The MSC cocultured with HUVEC could increase the VEGF levels,reduce TNF-α levels,as well as increase Bcl-2 mRNA expression but reduce the expression of Bax mRNA,HUVEC apoptosis was significantly decreased. Conclusions MSC can attenuate HUVEC apoptosis induced by ox-LDL,possibly through the increase of VEGF,reduction of TNF-α,and upregulation of Bcl-2 mRNA and downregulation of Bax mRNA,which provides a theoretical basis for MSC as a treatment for endothelial injury disease such as atherosclerosis.

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王双双,孔根现,杨升华,蒋知新,张清华.骨髓间充质干细胞拮抗氧化型低密度脂蛋白[J].中国动脉硬化杂志,2013,21(02):105~108.

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  • 收稿日期:2012-09-13
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