目的 探讨重组1型腺相关病毒(rAAV1)介导的SERCA2a基因转移对心力衰竭(HF)犬心功能的改善作用及机制.方法 选取20只健康雄性比格犬,随机分为对照组、HF组、HF+EGFP组和HF+SERCA2a组,检测各组犬心功能,采用TUNEL法和免疫组织化学法检测心肌细胞凋亡及MMP-9表达.结果 HF组和HF+EGFP组左室舒张期内径(LVDD)、左室收缩期内径(LVSD)和左室后壁厚度(LVPWD)明显高于对照组和HF+SERCA2a组,而射血分数(EF)明显低于对照组和HF+SERCA2a组(P<0.05);HF组和HF+EGFP组左室收缩压峰值(LVSP)和左室内压最大上升速率(+dp/dtmax)明显低于对照组和HF+SER-CA2a组,而左室舒张末压(LVEDP)和左室内压最大下降速率(-dp/dtmax)明显高于对照组和HF+SERCA2a组(P<0.05);HF+SERCA2a组心肌细胞凋亡指数明显低于HF组和HF+EGFP组(P<0.05);HF+SERCA2a组MMP-9光密度值高于对照组(P<0.05).结论 rAAV1介导的SER CA2a基因转移能有效改善HF犬心功能,其机制可能与抑制心肌细胞凋亡、下调MMP-9表达有关.%Objective To investigate the effect and mechanism of recombinant adenovirus associated vi-rus type 1 (rAAV1) mediated SERCA2a gene transfer on cardiac function in canine with heart failure (HF). Methods 20 healthy male beagle dogs were randomly divided into control group,HF group,HF+EGFP group and HF+SERCA2a group,5 dogs in each group. The canine cardiac function,apoptosis and MMP-9 expression in cardiac myocytes were detected by TUNEL and immunohistochemistry methods. Results The left ventricular dia-stolic diameter (LVDD),left ventricular systolic diameter (LVSD) and left ventricular posterior wall dimension (LVPWD)in the HF and HF+EGFP groups,were significantly higher than those of the control and HF+SERCA2a groups,and the ejection fraction(EF)in the former two groups was significantly lower than that of the control group and HF+SERCA2a group(P<0.05). The left ventricular systolic pressure(LVSP)and left ventricular maximal rate of pressure rise(+dp/dtmax)in the HF and HF+EGFP groups were both significantly lower than those of the control group and HF+SERCA2a group,while left ventricular end diastolic pressure(LVEDP)and left ventricular maximal rate of pressure decline(-dp/dtmax)significantly higher than those of the control and HF+SERCA2a groups(P<0.05). The apoptosis index of HF+SERCA2a group was significantly lower than that of group HF and group HF+EGFP(P<0.05). The MMP-9 light density of HF+SERCA2a group was significantly higher than that of the control group(P < 0.05). Conclusion RAAV1 mediated CA2a SER gene transfer can effectively improve the cardiac function of HF dog,probably by inhibiting the apoptosis of cardiac muscle cells and down-regulating the expression of MMP-9.
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