| 项 羽,汪 佩,王军奎,马彦鹏,潘 硕.AAV-9病毒转载sfrp1靶向干预wnt信号通路治疗心力衰竭大鼠分子机制研究[J].,2023,(12):2229-2233 |
| AAV-9病毒转载sfrp1靶向干预wnt信号通路治疗心力衰竭大鼠分子机制研究 |
| Molecular Mechanism of AAV-9 Virus Transfected sfrp1 Targeting Intervention of wnt Signaling Pathway in the Treatment of Heart Failure in Rats |
| 投稿时间：2022-12-05 修订日期：2022-12-28 |
| DOI：10.13241/j.cnki.pmb.2023.12.005 |
| 中文关键词: AAV-9病毒 可溶性卷曲相关蛋白1 wnt信号通路 心力衰竭 |
| 英文关键词: AAV-9 virus Soluble crimp related protein 1 Wnt signaling pathway Heart failure |
| 基金项目:陕西省创新人才推进计划-青年科技新星项目（2020KJXX-086） |
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| 中文摘要: |
| 摘要 目的：探讨腺病毒9（AAV-9）转载可溶性卷曲相关蛋白1（Sfrp1）靶向干预wnt信号通路治疗心力衰竭大鼠的效果和分子机制。方法：选择45只健康SD雄性大鼠作为研究对象，随机分为对照组、模型组和sfrp1组，各15只。模型组和sfrp1组采用左前降支动脉结扎手术建立慢性心力衰竭大鼠模型后，给予对照组和模型组大鼠经尾静脉注射生理盐水，给予sfrp1组大鼠经尾静脉注射AAV-sfrp1载体。分别在建模成功时和注射AAV-9病毒载体第28 d通过心脏超声评价各组大鼠心功能[左室射血分数（LVEF）、左室收缩期内径（LVIDS）和左室短轴缩短率（LVFS）]。采用酶联免疫吸附法检测腹主动脉血血清中Ⅰ型和Ⅲ型胶原水平。采用TUNEL法检测各组大鼠心肌细胞凋亡情况。采用Western blot技术检测心肌组织细胞中β-catenin、Dvl-1和α-SMA蛋白表达情况。结果：模型组和sfrp1组大鼠建模成功时的LVEF、LVFS均显著低于对照组，LVIDS显著大于对照组。注射AAV-9病毒载体后第28 d时sfrp1组大鼠LVEF和LVFS显著增加并显著大于模型组，LVIDS显著降低并显著低于模型组（P<0.05）。sfrp1组大鼠血清胶原Ⅰ和胶原Ⅲ水平以及心肌细胞凋亡比例均显著高于对照组，但显著低于模型组（P<0.05）。sfrp1组大鼠心肌组织中β-catenin、Dvl-1、α-SMA蛋白相对表达水平显著高于对照组，但显著低于模型组（P<0.05）。结论：AAV-9病毒转载sfrp1能够通过靶向抑制wnt信号通路以及抑制心肌胶原合成，降低心肌细胞凋亡，改善心力衰竭大鼠心脏功能。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the effect and molecular mechanism of adeno associated virus (AAV-9) transfection of soluble frizzled related protein 1 (Sfrp1) on wnt signaling pathway in rats with heart failure. Methods: Forty five healthy male SD rats were randomly divided into Matched group, model group and sfrp1 group with 15 rats each. The rats in the model group and sfrp1 group were injected with normal saline via tail vein and the rats in the Matched group and model group were injected with AAV sfrp1 carrier via tail vein after the rat model of chronic heart failure was established by ligation of left anterior descending artery. The cardiac function [left ventricular ejection fraction (LVEF), left ventricular systolic diameter (LVIDS) and left ventricular fractional shortening (LVFS)] of rats in each group were evaluated by echocardiography when the modeling was successful and on the 28th day after the injection of AAV-9 virus vector. The levels of type Ⅰ and type Ⅲ collagen in the blood serum of abdominal aorta were detected by enzyme-linked immunosorbent assay. TUNEL method was used to detect the apoptosis of myocardial cells in each group. The expression of β-catenin, Dvl-1 and α-SMA in myocardial cells was detected by Western blot. Results: LVEF and LVFS of model group and sfrp1 group were lower than those of Matched group, LVIDS was higher than that of matched group. LVEF and LVFS of rats in sfrp1 group were increased and larger than those in the model group on the 28th day after the injection of AAV-9 virus vector, and LVIDS was decreased and lower than that in the model group (P<0.05). The levels of serum collagen I and collagen III and the percentage of cardiomyocyte apoptosis in sfrp1 group were higher than those in the matched group, but lower than those in the model group (P<0.05). The relative expression levels of β-catenin, Dvl-1 and α-SMA protein in myocardium of rats in sfrp1 group were higher than those in matched group, but lower than those in model group (P<0.05). Conclusion: AAV-9 virus transfected sfrp1 can reduce cardiomyocyte apoptosis and improve cardiac function of rats with heart failure by targeting to inhibit wnt signaling pathway and myocardial collagen synthesis. |
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