17β-雌二醇对机械牵拉诱导心肌细胞integrin β1/FAK/p38 MAPK信号转导的影响  

Effects of 17β-estradiol on mechanical stretch-induced integrin β1/FAK/p38 MAPK signal pathway of cardiomyocyte hypertrophy

作　　者：刁爱芹[1] 潘爱萍[1] 王卉[1] 周瑞芳[1] 李晓洁[1] 张鹏[1] 李建涛[2] Diao Aiqin;Pan Aiping;Wang Hui;Zhou Ruifang;Li Xiaojie;Zhang Peng;Li Jiantao(Medical Institute of Taizhou Polytechnic College,Taizhou 225300;Department of Pathophysiology,NMU,Nanjing 211166,China)

机构地区：[1]泰州职业技术学院医学技术学院,江苏泰州225500 [2]南京医科大学病理生理学系,江苏南京211166

出　　处：《南京医科大学学报（自然科学版）》2018年第10期1357-1360,1408,共5页Journal of Nanjing Medical University(Natural Sciences)

基　　金：泰州市社会发展课题资助项目(TS201523);泰州职业技术学院重点科研课题资助项目(TZKY-15-8);泰州职业技术学院大学生创新项目(YJDC2015004)

摘　　要：目的:研究17β-雌二醇(17β-estradiol,E2)对体外机械牵拉诱导心肌细胞integrinβ1/FAK/p38 MAPK信号转导的影响。方法:以机械牵拉刺激体外培养的新生大鼠心肌细胞,建立心肌细胞肥大模型,采用免疫共沉淀方法检测integrinβ1和FAK的结合情况,Western blot方法检测FAK和p38 MAPK磷酸化水平的变化。结果:机械牵拉心肌细胞24 h后,integrinβ1和FAK的结合显著增加,FAK和p38 MAPK磷酸化水平亦明显增强。100 nmol/L E2预处理30 min可明显减轻机械牵拉诱导的心肌细胞integrinβ1和FAK的结合增加,抑制FAK和p38 MAPK磷酸化的水平增强,该效应可被雌激素受体非特异性拮抗剂ICI182780逆转。结论:100 nmol/L的E2能够抑制机械牵拉诱导心肌细胞肥大发生发展过程中integrinβ1对其下游FAK招募结合增加,降低FAK及p38MAPK的磷酸化活性,提示E2与雌激素受体结合后通过抑制integrinβ1/FAK/p38 MAPK信号转导途径的激活,从而发挥心血管保护作用。Objective：To investigate effects of 17β-estradiol（E2）on mechanical stretch-induced integrin β1/FAK/p38 MAPK signal pathway of cardiomyocyte hypertrophy. Methods：Cardiomyocyte from neonatal rats were cultured in vitro and cardiomyocyte hypertrophy was induced by mechanical stretch. The association of integrin β1 and FAK was evaluated by immunoprecipitation,and the phosphorylation of FAK and p38 MAPK were determined by Western blot. Results：Mechanical stretch for 24 h significantly increased the association of integrin β1 and FAK,and increased the phosphorylation of FAK and p38 MAPK. Pretreatment with 100 nmol/L E2 for 30 min significantly attenuated the increases in the association of integrin β1 and FAK which were attenuated by estrogen receptor antagonist ICI182780. Furthermore,E2 also decreased the levels of the phosphorylation of FAK and p38 MAPK induced by mechanical stretch,which were also attenuated by ICI182780. Conclusion：The combination of E2 and estrogen receptors can inhibit the activation of integrin β1/FAK/p38 MAPK signaling pathway induced by mechanical stretch to play a cardiovascular protective effect.

关 键 词：雌激素 机械牵拉 心肌细胞 INTEGRIN β1/FAK/p38 MAPK 

分 类 号：R393[医药卫生—基础医学]