摘要
目的探讨白蛋白微泡介导的pcDNA3.1-FKBP12.6质粒转染对心衰犬心功能及心肌病理变化的影响。方法28只快速起搏心衰犬分为2组。转染组以白蛋白微泡为载体,在超声破坏下将人工合成的pcDNA3.1-FKBP12.6质粒转染入心肌,以不含质粒的微泡作为对照组。两组又分为转染后4d(转染Ⅰ组)和14d(转染Ⅱ组)。分别在起搏器安置前、转染前、转染后,采用超声测量左室内径、心功能评价FKBP12.6基因对心衰的治疗效果。通过HE染色和透射电镜观察心肌病理变化。应用RT-PCR检测各组FKBP12.6基因的表达情况。结果超声微泡介导的转染可以提高心肌FKBP12.6 mRNA的表达。心肌病理显示转染组病变轻于对照组,而且未转染组病变进一步恶化。转染组EF、FS在第4天可见明显好转,并在14d时保持稳定,但一直低于正常水平。在第4天时转染组LVEDD与对照组无变化,而LVEDV下降(P=0.04),在14d时两指标与对照组比较均缩小(LVEDD和LVEDV的P值分别为0.012和0.005)。结论通过超声微泡介导转染FKBP12.6基因可以改善心脏功能,逆转心肌重塑,减轻心肌病理变化。
Objective To investigate the effect of gene transfection of FKBP12.6 on cardiac function and pathological changes of canine heart failure induced by rapid ventricular pacing. Methods Three weeks after onset of rapid ventricular pacing （250 beats/min）, 28 canines were divided into 4 groups. Either pcDNA3.1- FKBP12.6 plasmid encoding human FKBP12.6 gene（ transfection groupⅠ, Ⅱ ; observed at the 4th or 14th day respectively after trasnfection） or empty vector（ controlⅠ ,Ⅱ ） was transferred into myocardium under ultrasonic microbubble destruction. After the transfection, maintenance pacing at a reduced rate （190 beats/min） was continued until end-point of experiment. Echocadiographic data were collected three times （ before pacing, before transfection and endpoint）. The pathological change of myocardium is assessed by HE staining and electron microscope. Semiquantative RT-PCR identified FKBP12.6 expression in myocardium. Results Gene transfection of FKBP12.6 elevated expression of FKBP12.6 mRNA 3.4 folds at day 4 ,and 1.7 folds at day 14 respectively, compared with control group. The pathology indicated relative severe changes were observed in control groups and it further aggravated in group control Ⅱ. Cardiac function was significantly improved in transfection group Ⅰ and this effect was stable at least 2 weeks. Eject fraction （EF）, fractionar shorting （FS） are still lower than pre-pacing although they increase in transfection groups. Left ventricular end-diastolic diameter（LVEDD） and left ventricular end-diastolic volume（LVEDV） decreased at day 14 but LVEDD remained unchanged at day 4 compared with pre-transfection. Conclusion Gene transfection of FKBP12.6 improves cardiac function in the failing heart, reverses myocyte remodeling and promotes recovery from pathological changes. Thereby it is a novel gene therapy for human heart failure.
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2008年第5期431-434,共4页
Journal of Third Military Medical University
基金
国家自然科学基金(30371363)~~
