银杏内酯B对缺氧/复氧心肌细胞Caspase-3/PTEN/Akt通路及细胞增殖凋亡的影响  

Effects of ginkgolide B on Caspase-3/PTEN/Akt pathway and cell proliferation and apoptosis in hypoxia/reoxygenation cardiomyocytes

作　　者：陈海宇[1] 郑富臻[1] 翁国星[1] 鲍家银[1] 黄杰[1] 严李程 柯秋晴[2] CHEN Haiyu;ZHENG Fuzhen;WENG Guoxing;BAO Jiayin;HUANG Jie;YAN Licheng;KE Qiuqing(Department of Cardiovascular Surgery,Provincial Clinical School of Medicine,Fujian Medical University,Fujian Provincial Hospital,Fuzhou,350001,P.R.China;Department of Internal Medicine,Provincial Clinical School of Medicine,Fujian Medical University,Fujian Provincial Jinshan Hospital,Fuzhou,350001,P.R.China)

机构地区：[1]福建医科大学省立临床医学院、福建省立医院心血管外科,福州350001 [2]福建医科大学省立临床医学院、福建省立金山医院内科,福州350001

出　　处：《中国胸心血管外科临床杂志》2022年第12期1647-1652,共6页Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

基　　金：福建省自然科学基金面上项目(2019J01173);福建医科大学启航基金项目(2016QH104);福建省卫生计生中青年骨干人才培养项目(2017-ZQN-12);福建省立医院“创双高”火石基金项目(2020HSJJ15)。

摘　　要：目的探讨银杏内酯B(ginkgolide B,GB)对缺氧/复氧心肌细胞半胱氨酸蛋白酶-3(Caspase-3)/10号染色体缺失张力蛋白同源的磷酸酶基因(chromosome 10 deletion phosphatase-tension protein homologue,PTEN)/蛋白激酶B(protein kinase B,Akt)通路及细胞增殖凋亡的影响。方法体外培养H9C2细胞,对照组用无血清DMEM高糖培养基在37℃、5%CO_(2)条件下培养28 h,其余各组制备缺氧/复氧模型,GB低剂量组和GB高剂量组在缺氧/复氧前1 h分别用终浓度为50μmol/L和200μmol/L的GB预处理,卡维地洛组在缺氧/复氧前1 h用终浓度为10μmol/L的卡维地洛预处理。检测H9C2细胞增殖和细胞凋亡,同时检测H9C2细胞中乳酸脱氢酶(lactate dehydrogenase,LDH)、丙二醛(malondialdehyde,MDA)、活性氧(reactive oxygen species,ROS)、PTEN、Akt、磷酸化Akt(phosphorylated Akt,p-Akt)和Caspase-3水平。结果与对照组比较,其余各组H9C2细胞增殖率、PTEN、Akt和p-Akt水平降低,细胞凋亡率、LDH、MDA、ROS和Caspase-3水平升高(P<0.05);与缺氧复氧组比较,各GB剂量组和卡维地洛组H9C2细胞增殖率、PTEN、Akt和p-Akt水平升高,细胞凋亡率、LDH、MDA、ROS和Caspase-3水平降低,各GB剂量组呈剂量依赖性,但GB的作用强度不如卡维地洛(P<0.05)。结论GB通过激活Caspase-3/PTEN/Akt通路,抑制缺氧/复氧H9C2细胞凋亡,促进H9C2细胞增殖。Objective To investigate the effect of ginkgolide B(GB)on cysteinyl aspartate specific proteinase-3(Caspase-3)/chromosome 10 deletion phosphatase-tension protein homologue(PTEN)/protein kinase B(Akt)pathway and cell proliferation and apoptosis in hypoxia/reoxygenation cardiomyocytes.Methods H9C2 cells were cultured in vitro.A control group was cultured in serum-free DMEM high glucose medium at 37°C and 5%CO2 for 28 hours.The remaining groups were prepared with hypoxia/reoxygenation models.A GB low-dose group and a GB high-dose group were treated with GB pretreatment with final concentration of 50μmol/L and 200μmol/L respectively at 1 h before hypoxia/reoxygenation.A carvedilol group was treated with carvedilol of a final concentration of 10μmol/L at 1 h before hypoxia/reoxygenation.The proliferation and apoptosis of H9C2 cells were detected,and the levels of lactate dehydrogenase(LDH),malondialdehyde(MDA),reactive oxygen species(ROS),PTEN,Akt,phosphorylated Akt(p-Akt)and Caspase-3 in H9C2 cells were also detected.Results Compared with the control group,the proliferation rate of H9C2 cell,and the levels of PTEN,Akt and p-Akt in other groups decreased,and the apoptosis rate,and the levels of LDH,MDA,ROS and Caspase-3 increased(P<0.05).Compared with the hypoxia/reoxygenation group,the proliferation rate of H9C2 cell,and the levels of PTEN,Akt and p-Akt in all GB dose groups and the carvedilol group increased;the apoptosis rate,and the levels of LDH,MDA,ROS and Caspase-3 decreased,and the effect of GB was in a dose dependent manner;however,the effect of GB was not as strong as carvedilol(P<0.05).Conclusion GB can inhibit H9C2 cell apoptosis and promote H9C2 cell proliferation by activating Caspase-3/PTEN/Akt pathway.

关 键 词：银杏内酯B 缺氧/复氧 心肌细胞 Caspase-3/PTEN/Akt通路 细胞增殖 细胞凋亡 

分 类 号：R542.22[医药卫生—心血管疾病]