超声介导SDF-1α基因转染急性心肌梗死大鼠心脏对非靶组织的影响

发布时间：2018-05-03 09:25

本文选题：靶向微泡破坏技术 + 基质细胞衍生因子-1α　；参考：《新疆医科大学》2017年硕士论文

【摘要】：目的:利用超声靶向微泡破坏(Ultrasound targeted microbubble destruction,UTMD)技术介导外源性基因修复受损的靶器官和组织的研究正在加速发展,但基因转染修复靶器官的同时对非靶组织的影响情况研究较少,而超声、微泡及重组腺病毒联合介导基因在非靶组织中的转染未见报道,本研究旨在评价超声、微泡及重组腺病毒联合介导外源性基质细胞衍生因子1α(Stromal Cell-derived Factor-1α,SDF-1α)基因转染急性心肌梗死(Acute Myocardial Infarction,AMI)大鼠心脏时在非靶组织肝脏、肺脏及肾脏的转染情况。方法:成功构建AMI模型的40只SD大鼠按照查随机数字表的方法将其完全随机分为4组:单纯超声辐照组(M+U组/对照组,n=10);超声辐照+载pAd-EGFP/SDF-1α(生物素化的共表达绿色荧光蛋白和SDF-1α的重组腺病毒)基因微泡给药1天组(M+S1+U组,n=10)、连续给药2天组(M+S2+U组,n=10)及连续给药3天组(M+S3+U组,n=10)。AMI术后7天,激光共聚焦显微镜观察非靶组织肝脏、肺脏及肾脏中绿色荧光蛋白的表达情况。结果:增强型绿色荧光蛋白分别在肺脏、肝脏及肾脏中的表达面积比如下(%area):M+U:0,0,0;M+S1+U:2.57±0.88,2.31±0.77,2.30±0.80;M+S2+U:2.97±0.94,2.89±1.00,2.77±0.82;M+S3+U:3.01±0.71,2.98±0.86,2.89±0.79。所有给药组与对照组相比差异均具有统计学意义(P㩳0.05),但给药一、二及三天组间差异无统计学意义。结论:超声、微泡及重组腺病毒联合介导外源性SDF-1α基因转染AMI大鼠心脏的同时,非靶组织肝脏、肺脏及肾脏也会被转染,而且随着给药天数的增加,转染亦呈增加趋势,但靶基因在非靶组织中的转染与给药天数并非呈线性相关,即随着给药天数的增加,靶基因在非靶组织中的转染并未产生显著的累积效应。
[Abstract]:Objective: the study of transgene repair of damaged target organs and tissues mediated by ultrasound targeted microbubble destruction of ultrasound targeted microbubble destructionwas accelerated, but the effect of gene transfection on non-target tissues was less studied. However, the transfection of genes mediated by ultrasound, microbubbles and recombinant adenovirus in non-target tissues has not been reported. Transfection of exogenous stromal Cell-derived Factor-1 伪 Cell-derived Factor-1 伪 -SDF-1 伪 gene into the heart of acute myocardial infarction (AMI) rats by microbubble and recombinant adenovirus in non-target liver, lung and kidney. Methods: forty SD rats who successfully constructed AMI model were randomly divided into 4 groups according to the method of random digital table: pure ultrasound irradiation group, mu group / control group, ultrasound irradiation pAd-EGFP/SDF-1 伪 (biotin coexpression green) Fluorescent protein and recombinant adenovirus of SDF-1 伪) gene microbubble administration group was treated with MS1U for 1 day, group M S 2 U for 2 days, group M S 3 U for 3 days, group M S 3 U for 7 days after operation, and group M S 3 U for 3 days for 7 days after operation. The expression of green fluorescent protein (GFP) in liver, lung and kidney was observed by confocal laser microscopy. Results: the expression areas of enhanced green fluorescent protein in lung, liver and kidney were as follows: a: M: M: U: 0: 0. M S1: U: 2.57 卤0.88 卤2.31 卤0.80 MS2: 2.97 卤0.94U 2.89 卤1.002.77 卤0.82mS3 U3.01 卤0.71U: 2.98 卤0.862.89 卤0.79. Compared with the control group, the difference of all groups was statistically significant, but there was no significant difference between the first, second and third day of administration. Conclusion: ultrasound, microbubble and recombinant adenovirus mediated exogenous SDF-1 伪 gene transfection into the heart of AMI rats, while non-target liver, lung and kidney were also transfected, and the transfection showed an increasing trend with the increase of administration days. However, the transfection of target genes in non-target tissues was not linearly correlated with the days of administration, that is, the transfection of target genes in non-target tissues did not produce a significant cumulative effect with the increase of administration days.
【学位授予单位】：新疆医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R542.22;R445.1

【相似文献】