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目的:探讨白蛋白微泡介导的外源性pcDNA3.1-FKBP12.6质粒转染对心衰犬的治疗作用。方法: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质粒转染入快速起搏心衰犬心肌中。分别在转染后第4、14d,通过超声和有创血流动力学检查测定左室内径和心功能,同时检测血浆心钠肽(ANP)、脑钠肽(BNP),评价FK12.6结合蛋白(FKBP12.6)基因对心衰的治疗效果。应用RT-PCR检测各组FK-BP12.6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。射血分数(EF)、缩短分数(FS)、血流动力学指标及血浆ANP、BNP在第4d可见明显好转,并在14d时保持稳定,但EF、FS和心输出量(CO)一直低于正常水平。在第4d时LVEDD无变化,而左室舒张末期容积(LVEDV)下降(P<0.05),在14d时2指标与对照组比较均缩小(P<0.05,P<0.01)。结论:通过超声微泡介导转染FKBP12.6基因可以改善心脏功能,是心衰基因治疗的新手段。
Objective: To investigate the therapeutic effect of albumin-mediated microbubble-mediated exogenous pcDNA3.1-FKBP12.6 plasmid transfection on heart failure dogs. Methods: The recombinant plasmid pcDNA3.1-FKBP12.6 was transfected into the myocardium of fast pacemaker dogs by using albumin microbubbles as carrier. The left ventricular diameter and cardiac function were measured by ultrasound and invasive hemodynamic tests on the 4th and 14th day after transfection. Plasma ANP and BNP were also measured to evaluate the effect of FK12.6 binding Protein (FKBP12.6) Gene Therapy for Heart Failure. The expression of FK-BP12.6 gene in each group was detected by RT-PCR. RESULTS: Ultrasound-mediated microbubble-mediated transfection increased myocardial FKBP12.6 mRNA expression. The ejection fraction (EF), shortening fraction (FS), hemodynamics, plasma ANP and BNP were significantly improved on day 4 and remained stable on day 14, but EF, FS and cardiac output (CO) At normal level. There was no change in LVEDD and left ventricular end-diastolic volume (LVEDV) at 4 days (P <0.05), but both indicators were decreased at 14 days (P <0.05, P <0.01). Conclusion: Ultrasound-mediated microbubble-mediated FKBP12.6 gene therapy can improve cardiac function, which is a new method of gene therapy for heart failure.