| 常学锋,曲 萌,邹德利,何援越,赵东明,王思文,石 贺.Sfrp1通过阻断Wnt信号通路减轻血管紧张素Ⅱ诱导的心脏损伤并促进自噬的研究[J].,2023,(20):3820-3825 |
| Sfrp1通过阻断Wnt信号通路减轻血管紧张素Ⅱ诱导的心脏损伤并促进自噬的研究 |
| Sfrp1 Attenuates Angiotensin II-induced Cardiac Injury and Promotes Autophagy by Blocking the Wnt Signaling Pathway |
| 投稿时间：2023-04-20 修订日期：2023-05-15 |
| DOI：10.13241/j.cnki.pmb.2023.20.004 |
| 中文关键词: Sfrp1 心肌肥厚 凋亡 自噬 Wnt信号通路 |
| 英文关键词: Sfrp1 Myocardial hypertrophy Apoptosis Autophagy Wnt signaling pathway |
| 基金项目:吉林省教育厅"十三五"科学技术项目（JJKH20200056KJ）；吉林省卫生与健康技术创新项目（2020J018）；吉林市医疗卫生指导性计划项目（20210409062） |
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| 中文摘要: |
| 摘要 目的：本研究旨在评估Sfrp1在血管紧张素II诱导的心肌肥厚中的心脏保护作用，并探讨其与自噬和Wnt信号通路相关的可能机制。方法：利用重组AAV9载体将Sfrp1导入Ang II诱导的肥厚型H9C2心肌细胞。用CCK8测定细胞活力。流式细胞仪检测细胞凋亡率。用显微照片记录肥厚细胞大小的变化。western blot检测Sfrp1、Bcl-2、Bax、CytC、Caspase-3、P62、ATG5、Beclin、LC3、β-catenin和DVL1的蛋白表达。通过qRT-PCR检测β-连环蛋白和DVL1的mRNA表达。自噬抑制剂3-MA也用于验证治疗过程中自噬的参与。结果：（1）Sfrp1成功转染H9C2细胞，其过度表达减轻了心肌肥厚。（2）经过AAV9-Sfrp1预处理可减少肥厚心肌的细胞凋亡，可逆转Ang II组自噬相关蛋白（p62、ATG5、Beclin、LC3）的表达；（3）自噬在治疗心肌肥厚过程中的作用通过可自噬抑制剂3-MA来证实。（4）激活的Wnt信号（β-连环蛋白，DVL1）也被AAV9-Sfrp1抑制。结论：Sfrp1通过Wnt信号通路促进细胞自噬，从而保护心肌细胞免受肥厚性损伤和凋亡，这为Sfrp1对心肌肥厚的心肌保护作用机制提供了一个重要的视角。 |
| 英文摘要: |
| ABSTRACT Objective: To evaluate the cardioprotective effect of Sfrp1 in angiotensin II-induced cardiac hypertrophy and to explore its possible mechanism related to autophagy and Wnt signaling pathway. Methods: Sfrp1 was introduced into Ang II-induced hypertrophic H9C2 cardiomyocytes by recombinant AAV9 vector. Cell viability was measured by CCK8. The apoptosis rate was detected by flow cytometry. Changes in the size of hypertrophic cells were recorded by microphotography. Western blot was used to detect the protein expression of Sfrp1, Bcl-2, Bax, CytC, Caspase-3, P62, ATG5, Beclin, LC3, β-catenin and DVL1. The mRNA expression of β-catenin and DVL1 was detected by qRT-PCR. The autophagy inhibitor 3-MA was also used to verify the involvement of autophagy during treatment. Results: (1) Sfrp1 was successfully transfected into H9C2 cells, and its overexpression reduced cardiac hypertrophy. (2) AAV9-Sfrp1 pretreatment can reduce the apoptosis of hypertrophic myocardium and reverse the expression of autophagy-related proteins ( p62, ATG5, Beclin, LC3 ) in Ang II group. (3) The role of autophagy in the treatment of cardiac hypertrophy was confirmed by the autophagy inhibitor 3-MA. (4) The activated Wnt signaling ( β-catenin, DVL1 ) was also inhibited by AAV9-Sfrp1. Conclusion: Sfrp1 promotes autophagy through Wnt signaling pathway, thereby protecting cardiomyocytes from hypertrophic injury and apoptosis, which provides an important perspective for the myocardial protection mechanism of Sfrp1 on myocardial hypertrophy. |
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