rAAV1介导的SER CA2a基因转移对犬心力衰竭心功能改善作用

发布时间：2018-08-05 17:37

【摘要】：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(P0.05);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(P0.05);HF+SERCA2a组心肌细胞凋亡指数明显低于HF组和HF+EGFP组(P0.05);HF+SERCA2a组MMP-9光密度值高于对照组(P0.05)。结论 rAAV1介导的SERCA2a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。
[Abstract]:Objective to investigate the effect and mechanism of SERCA2a gene transfer mediated by recombinant adeno-associated virus (rAAV1) on cardiac function in (HF) dogs with heart failure. Methods Twenty healthy male Beagle dogs were randomly divided into two groups: control group (HF group), HF EGFP group and HF SERCA2a group. Cardiac function was measured in each group. Myocardial apoptosis and MMP-9 expression were detected by TUNEL and immunohistochemistry. Results left ventricular diastolic diameter (LVDD), left ventricular systolic diameter (LVSD) and left ventricular posterior wall thickness (LVPWD) in HF group and HF EGFP group were significantly higher than those in control group and HF SERCA2a group. However, the ejection fraction (EF) was significantly lower than that in the control group and HF SERCA2a group (P0.05). The peak left ventricular systolic pressure (LVSP) and the maximum left ventricular pressure rising rate (dp/dtmax) in HF EGFP and HF EGFP groups were significantly lower than those in control group and HF SER-CA2a group. However, left ventricular end-diastolic pressure (LVEDP) and left ventricular pressure (-dp / DT max) were significantly higher than those in control group and HF SERCA2a group (P0.05). The myocardial apoptosis index in HF SERCA2a group was significantly lower than that in HF group and HF EGFP group (P0.05). MMP-9 optical density in HF SERCA2a group was significantly higher than that in control group (P0.05). Conclusion rAAV1 mediated SERCA2a gene transfer can effectively improve cardiac function in HF dogs. The mechanism may be related to inhibition of cardiomyocyte apoptosis and down-regulation of MMP-9 expression.
【作者单位】：广东医科大学附属医院心血管内科一区;
【基金】：国家自然科学基金(编号:71373058)
【分类号】：R541.6

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