共载体AAV-PR39-ADM治疗缺血性心脏病

目的:探讨共载体AAV-PR39-ADM分泌表达血管生成肽(PR39)与血管扩张肽(ADM)对SD大鼠心肌缺血再灌注损伤的作用。方法:选健康成年雄性SD大鼠36只,体重平均为280 g±20 g,随机分为假手术组(SO)、治疗组(TR)与对照组(I/R),每组各12只。治疗组大鼠心肌注射共载体AAV-PR39-ADM感染心肌7天后行B超检查,测量记录左室壁厚度及射血分数(EF%),左室收缩末压(LVSP),左室内压最大上升下降速率(±dp/dt max)评价作为心脏功能指标。对照组建立缺血再灌注损伤模型,假手术组只穿线不结扎且两组行相同检测。速取处死大鼠心肌行masson染色测量心肌梗死面积。结果:治疗组明显高于对照组,其射血分数、左室内收缩末压、最大上升速率,最大下降速率、梗死面积分别为:EF%(50.4±6.3),(29.8±10.5),P0.05;LVSP:(116±4.2),(101±3.7),P0.05;+dp/dt max:(2859±365),(2137±191),P0.05;-dp/dtmax:(2186±107),(1886±124),P0.05;IS%:(29.3±4.6),(24.6±2.2),P0.05。结论:共载体AAV-PR39-ADM能够显著恢复心肌缺血损伤引起的左室内压下降,提高心肌收缩能力,提高射血分数并明显缩小心肌梗死范围。

Co-integrated Vector of AAV-PR39-ADMTherapy Ischemic Heart Disease

Objective:To discuss the curative effect of the co-integrated vector of AAV-PR39-ADM which secret angiogenesis peptide (PR39) and Adrenomedullin(ADM) on a rat ischemia-reperfusion injury model.Methods:36 healthy adult male SD rats, weight 280g± 20g were randomly divided into sham-operation(SO), the treatment group (TR) and control group (I/R) each12. Ischemia-reperfusion injury model was established in both TR group and I/R group and co-integrated vector of AAV-PR39-ADMwas injected into the injured myocardiumof the treatment group rats. Echocardiographic measurement and record left ventricular systolic pressure (LVSP), maximal rate of rise of ventricular pressure (+dp/dt max), maximal rate of decline of ventricular pressure (-dp/dt max) and ejection fraction (EF %) were the treatment group rat of co-integrated vector of AAV-PR39-ADM transshipment myocardium after 7 days. The sham group was operated without coronary artery ligation. Hearts were speedy extracted after the execution of the rats, MASSON staining was carried out in the experiment.Results:The ejection fraction, left ventricular systolic pressure, maximum rate of left ventricular pressure rise or fall of the treatment group were significantly higher than those in control group EF%(50.4± 6.3), (29.8± 10.5), P<0.05; LVSP: (116± 4.2), (101± 3.7), P<0.05; +dp/dt max: (2859± 365), (2137± 191), P<0.05; -dp/dtmax: (2186± 107), (1886± 124), P<0.05; IS%: (29.3± 4.6), (24.6± 2.2), P<0.05.].Conclusion:Co-integrated vector of AAV-PR39-ADMsignificantly attenuated the declines of LVSP, increased the myocardial contraction ability, improved the ejection fraction and obviously reduced infarct size.