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超声微泡联合核定位信号促进SDF1α基因转染治疗兔心肌梗死
冯闯丽
0
(武汉大学人民医院超声科)
摘要:
【摘要】 目的 探讨超声辐照下携基质衍生因子1(SDF1α)基因的胞膜核膜双靶向阳离子微泡载体系统促进内源性干细胞归巢的机制。方法 构建双靶向阳离子微泡载体系统及携SDF1α阳离子微泡载体系统,分别于体外转染人脐静脉血管内皮细胞(HUVEC)并检测SDF1α质粒入胞率、入核率及SDF1α基因表达;进而构建心梗兔模型,造模成功后随机分为三组进行SDF1α基因转染:A组:携SDF1α双靶向阳离子微泡载体组;B组:携SDF1α阳离子微泡载体组;C组:对照组。分别于基因转染后3天和4周后检测SDF1α基因表达、干细胞标志物和血管新生效应。结果 体外实验中,超声辐照下,与携SDF1α阳离子微泡载体系统比较,携SDF1α双靶向阳离子微泡载体系统SDF1α质粒入胞率与其无显著差异(P>005),但入核率和SDF1α蛋白表达显著增高(P<001);体内实验显示,与阳离子微泡载体组及对照组比较,双靶向阳离子微泡载体组家兔心肌组织中SDF1α蛋白显著增高、干细胞标志物阳性染色显著增强、毛细血管密度显著增加(P<001)。结论 超声辐照下携SDF1α的胞膜核膜双靶向阳离子微泡载体系统能有效提高SDF1α基因载体转染效率,表达足量的SDF1α蛋白并发挥其干细胞诱导剂作用,从而促进内源性干细胞归巢并促进局部血管新生。
关键词:  超声微泡  干细胞归巢  阳离子微泡  基因转染  SDF 1α  NF κB
DOI:
基金项目:国家自然科学基金(81101058;81471674;81501495)
The ultrasound microbubbles combined the nuclear location signal promote SDF 1α gene transfection to treat the infarcted myocardium of rabbits
FENG Chuangli
(Department of Ultrasound, Renmin Hospital of Wuhan University)
Abstract:
【Abstract】 Objective To evaluate the mechanisms of endogenous stem cell homing improvement by cytoplasmic and nuclear membrane double targeted cationic microbubbles carrying SDF1α gene combined with ultrasonic irradiation.Methods The double targeted cationic microbubbles carrier system and cationic microbubbles carrying SDF1α gene were constructed. SDF1α gene was transfected to the human umbilical vein endothelial cell in vitro and efficiency of SDF1α gene transfection was detected including the SDF1αplasmid cellularimport rate, the SDF1αplasmidnuclear import rate and gene expression of SDF1α protein. Then the myocardial infarction rabbits models were built and divided randomly into A group, B group and C group. A group was treated with double targeted cationic microbubbles carrying SDF1αgroup. B group was treated with cationicmicrobubbles carrying SDF1αgroup. C group was control group. 3 days and 4 weeks after gene transfection, gene expression of SDF1α gene, stem cell markers and angiogenesis effects were detected respectively.Results In vitro, under the ultrasonic irradiation, compared with the cation microbubbles carrying SDF1α system, there was no difference in the SDF1αplasmidcellular import rate between the cation microbubbles carrying SDF1α system and the double targeted cationic microbubbles carrying SDF1α system, while the latter had the higher the SDF1αplasmidnuclear import rate and gene expression of SDF1α protein. In vivo, compared with thecationic microbubble carrying SDF1αgroup and control group, SDF1α protein expression, stem cell marker positive staining and capillary density in rabbits’ myocardium increased significantly in the double targeted cationic microbubble carrying SDF1αgroup.Conclusion Cytoplasmic and nuclear membrane double targeted cationic microbubbles carrying SDF1α gene combined with ultrasonic irradiation can improve the SDF1α gene transfection efficiency effectively, which induces the sufficient expression of SDF1α protein, playsa role of stem cells inducer, and then promotes endogenous stem cells homing and angiogenesis.
Key words:  Ultrasoand microbubbles  Stem cell homing  Cationic microbubble  Gene transfection  SDF 1α  NF κB

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