中文摘要：

目的：探讨重组9型腺相关病毒（rAAV9）携带 FrzA 基因转导对心肌细胞缺血缺氧模型 Wnt 信号通路活性的抑制作用及心肌细胞凋亡的影响。方法分离培养 SD 大鼠心肌细胞，将 rAAV9携带 FrzA 基因转导至心肌细胞，在 rAAV9表达高峰时建立心肌细胞缺血缺氧模型。随机分为空白组、缺血缺氧组、缺血缺氧＋rAAV9-CMV-eGFP 组（空病毒组）、缺血缺氧＋rAAV9-CMV-FrzA 组（FrzA 组）。采用 RT-PCR 检测各组心肌目的基因 FrzA的表达；Western blotting 测定心肌细胞 Wnt 信号通路关键分子 Dvl-1、β-catenin、c-Myc 水平及凋亡相关蛋白 Bcl-2、Bax 的表达。结果 rAAV9转染第5天，目的基因 FrzA 在心肌细胞中高表达（P ＜0．05）。缺血缺氧组、空病毒组、FrzA 组 Wnt 信号通路关键分子 Dvl-1、β-catenin、c-Myc 表达及凋亡蛋白 Bax／Bcl-2值较空白组明显升高（P 均＜0．05）。FrzA 组心肌细胞中 Wnt 信号通路关键分子 Dvl-1、β-catenin、c-Myc 表达及凋亡蛋白 Bax／Bcl-2值低于缺血缺氧组、空病毒组（P 均＜0．05）。结论 rAAV9介导的 FrzA 基因转导可有效干预 Wnt 信号通路，抑制其活性，从而减轻心肌细胞凋亡。

英文摘要：

Objective To investigate the effects of recombinant adeno-associated virus type 9 （rAAV9）carrying FrzA gene transduction in inhibiting Wnt signaling pathway activity and on myocardial apoptosis of cardiomyocytes in rat models with ischemia-hypoxia.Methods The myocardial cells of SD rats were isolated and cultured.A recombinant AAV9 vector carrying FrzA gene was transfected into cardiomyocytes and then a hypoxia model was created.We divided them into four groups：control group,ischemia-hypoxia group,ischemia-hypoxia ＋empty virus （rAAV9-CMV-GFP）group （empty virus group）and ischemia-hypoxia ＋rAAV9-CMV-FrzA group （FrzA group）.RT-PCR was used to detect the expression of tar-get gene FrzA,and Western blotting was applied to detect the levels of Dvl-1,β-catenin and c-Myc as well as expression of apoptosis-related proteins Bcl-2 and Bax.Results On the fifth day after virus transfection,the FrzA target gene was highly expressed in cardiomyocytes （all P 〈0.05）.The expression of Wnt signaling pathway molecules Dvl-1,β-catenin and c-Myc was significantly higher in the ischemia-hypoxia group,empty virus group and FrzA group,and the ratio of Bax/Bcl-2 was also higher than that of the control group （all P 〈0.05）.The expression of Wnt signaling pathway molecules Dvl-1,β-catenin and c-Myc was significantly lower in FrzA group,and the ratio of Bax/Bcl-2 was also lower than that of the ische-mia-hypoxia group and empty virus group （all P 〈0.05）.Conclusion rAAV9 carrying FrzA gene can effectively inter-vene the Wnt signaling pathway and inhibit its activity and thus reduce the apoptosis of cardiomyocytes.