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成纤维细胞生长因子21对缺氧复氧心肌细胞的保护作用及机制研究
许卫攀,吴勇波,张凯,陈志强,蔡振璇
0
(鄂东医疗集团黄石市中心医院心血管内科·湖北理工学院附属医院)
摘要:
【摘要】 目的 探讨成纤维细胞生长因子21(FGF21)对缺氧复氧(H/R)心肌细胞的保护作用及对PI3K/AKT通路的影响。方法 重组腺病毒载体AdFGF21诱导原代心肌细胞过表达FGF21。腺病毒转染心肌细胞后构建H/R损伤模型(3h缺氧联合3h复氧)。实验分为对照组(Con组)、H/R组、H/R+AdGFP组、H/R+AdFGF21组4组。心肌细胞存活率评估细胞损伤程度;SOD/MDA检测联合DHE荧光染色评估氧化应激反应(ROS);流式细胞术评估细胞凋亡;Western blot检测相关蛋白水平。在机制探讨实验中给予PI3K/AKT抑制剂(LY294002)进行干预。结果 与Con组相比,H/R损伤后FGF21蛋白表达显著下调,并伴随心肌细胞活性降低、ROS与凋亡反应激活。腺病毒介导的心肌细胞过表达FGF21能够明显抑制H/R损伤,表现为细胞活力、ROS与凋亡反应均有不同程度改善。FGF21心肌细胞过表达能够增加PI3K/AKT磷酸化水平,而抑制PI3K/AKT通路后FGF21过表达介导的细胞保护功能被逆转。结论 FGF21主要通过PI3K/AKT依赖性途径改善心肌细胞H/R损伤。
关键词:  FGF21  缺氧复氧  凋亡  氧化应激  PI3K  AKT
DOI:
基金项目:国家自然科学基金项目(81470387);2017年湖北省科技计划项目(2017CFB211)
The protective effects and potential mechanisms of FGF21 on myocardial hypoxia/reoxygenation injury
XU Weipan,WU Yongbo,ZHANG Kai,CHEN Zhiqiang,CAI Zhenxuan
(Department of Cardiology, Huangshi Central Hospital of Edong Healthcare Group,The Affiliated Hospital of Hubei Polytechnic University))
Abstract:
【Abstract】 Objective To measure the roles of fibroblast growth factor 21 (FGF21) on hypoxia/reoxygenation (H/R)treated cardiomyocytes and the potential mechanisms. Methods Adenoviral vector encoding FGF21 (AdFGF21) was used to elevate FGF21 in cultured neonatal rat cardiomyocytes. The experiments were assigned into four groups: control group, H/R group, H/R+AdGFP group and H/R+ AdFGF21 group. Three hours of hypoxia and 3h of reoxygenation were performed to cause H/R injury followed after viral transfection. Cell viability was detected by CCK8 assay. The apoptosis, ROS and molecular alternations were systematically estimated. Moreover, the specific PI3K/AKT inhibitor (LY294002) was added in mechanistic detections. Results In comparison with the control group, H/R resulted in the downregulation of FGF21 followed by the worsened cardiomyocytes damage, as exhibited by the decrease of viability and the promotion of ROS and apoptosis. However, above parameters induced by H/R were attenuated by FGF21 overexpression. Mechanistic experiments showed that FGF21 elevation enhanced the levels of pPI3K/AKT, and blocking PI3K/AKT with its specific inhibitor LY294002 dampened the H/Rlimited effects of FGF21. Conclusion FGF21 ameliorates myocardial H/R injury in part via a PI3K/AKTdependent way.
Key words:  FGF21  H/R  Apoptosis  ROS  PI3K  AKT

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