骨髓间充质干细胞移植多器官功能不全综合征兔心、肝、肺器官中凋亡因子Apaf-1的表达

Apoptotic protease activating factor-1 expression in the heart,liver and lung of rabbits with multiple organ dysfunction syndrome following bone marrow mesenchymal stem cells transplantation

背景:研究证明多器官功能不全综合征的发病及其器官组织损伤与细胞凋亡和坏死有关,而近年来骨髓间充质干细胞作为种子细胞在修复领域已初现成效。目的:观察骨髓间充质干细胞移植对多器官功能不全综合征兔受累脏器组织细胞凋亡蛋白酶活化因子1表达的影响。方法:实验组建立两次打击多器官功能不全综合征动物模型,进行兔自体骨髓间充质干细胞体外培养、扩增、鉴定,慢病毒转基因标记GFP,经股动脉移植,并设立模型对照组及正常组。组织切片观察骨髓间充质干细胞在多器官功能不全综合征动物模型宿主内的存活情况,RT-PCR测定骨髓间充质干细胞移植前后凋亡因子Apaf-1在心、肝、肺重要脏器中的表达。结果与结论:实验组兔肝、肺脏器组织内有慢病毒转基因标记GFP的骨髓间充质干细胞存在。RT-PCR结果显示正常组织心、肝、肺中均有Apaf-1mRNA表达,且模型对照组心、脾、肾Apaf-1mRNA表达较正常组明显增加,而实验组兔心、脾、肾组织中Apaf-1mRNA表达下降。说明骨髓间充质干细胞具有良好的生物学活性,移植后的骨髓间充质干细胞能够定植在多器官功能不全综合征兔的受损脏器组织内,并下调Apaf-1mRNA的表达,提示骨髓间充质干细胞移植有望为多器官功能不全综合征提供新的治疗方法。

BACKGROUND：The multiple organ dysfunction syndrome （MODS） onset and organ tissue injury are associated with cell apoptosis and necrosis.However, bone marrow mesenchymal stem cells （BMSCs） as seed cells are effective in repair field.OBJECTIVE：To observe BMSCs transplantation effects on apoptotic protease-activating factor 1 （Apaf-1） expression in involved organs of rabbits with MODS.METHODS：Two-hit animal model of MODS was established in the experimental group.Rabbit BMSCs were cultured, amplified and identified in vitro, and then labeled with GFP by lentivirus.BMSCs were transplanted via the femoral artery.We also set model control and normal groups.The survival of BMSCs in model of MODS was observed.Apaf-1 gene expression was detected in the heart, liver and lung prior to and following transplantation using RT-PCR.RESULTS AND CONCLUSION：Lentiviral transgenic GFP marker presence of BMSCs was visible in the rabbit liver and lung in the experimental group.RT-PCR results showed that Apaf-1 mRNA expression was determined in the heart, liver and lung tissues of normal group, and significantly increased in the heart, spleen and kidney of model control group.Apaf-1 mRNA expression was decreased in the rabbit heart, spleen and kidney of experimental group.These indicated that BMSCs have good biological activity.Transplanted BMSCs could implant in the damaged organs of rabbits with MODS, downregulate Apaf-1 mRNA expression, which suggested that BMSCs transplantation can provide a new therapeutic method for MODS.