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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 effects of pcDNA3.1-FKBP12.6 plasmid transfection mediated by albumin microbubbles on cardiac function and pathological changes of heart failure dogs. Methods 28 fast pacing heart failure dogs were divided into two groups. Transfection group to albumin microbubbles as a carrier, under the ultrasound damage will be artificial synthesis of pcDNA3.1-FKBP12.6 plasmid transfected into the myocardium to plasmid-free microbubbles as a control group. Two groups were divided into 4 days after transfection (group Ⅰ) and 14 days (group Ⅱ). Respectively before placement of the pacemaker, before transfection, after transfection, the left ventricular diameter was measured by ultrasound, and the cardiac function was evaluated for the therapeutic effect of FKBP12.6 gene on heart failure. Pathological changes of myocardium were observed by HE staining and transmission electron microscopy. The expression of FKBP12.6 gene in each group was detected by RT-PCR. Results Ultrasound-mediated microbubble-mediated transfection increased myocardial FKBP12.6 mRNA expression. Myocardial pathology showed that the lesion in the transfected group was lighter than that in the control group, and the pathological changes in the untransfected group were further worsened. Transfection group EF, FS visible improvement on the 4th day, and remained stable at 14d, but has been below the normal level. At day 4, LVEDD in the transfection group was unchanged from that in the control group, while LVEDV was decreased (P = 0.04). Both indexes were reduced on the 14th day compared with the control group (P values of LVEDD and LVEDV were 0.012 and 0.005, respectively). Conclusion Ultrasound-mediated microbubble mediated FKBP12.6 gene can improve cardiac function, reverse myocardial remodeling, reduce myocardial pathological changes.