HDAC9通过下调PDE4b表达参与调控小鼠心肌肥厚  

HDAC9 down-regulates PDE4b in cardiac hypertrophy remodeling

作　　者：曹腾飞 孙中新 张俊[1] CAO Tengfei;SUN Zhongxin;ZHANG Jun(Department of Cardiology, The First Hospital of Chengdu, Chengdu 610016, China;The Third Hospital of Chengdu, Chengdu 610012, China)

机构地区：[1]成都市第一人民医院心内科,四川成都610016 [2]成都市第三人民医院,四川成都610012

出　　处：《西部医学》2022年第3期347-351,共5页Medical Journal of West China

摘　　要：目的探讨心肌肥厚性重构可能分子机制。方法选取8周龄清洁级雄性C57小鼠18只,随机分为升主动脉缩窄术(TAC)组和对照组(SHAM组),每组9只。TAC组给予升主动脉缩窄术(TAC术)构建心肌肥厚模型。SHAM组给予假手术。术后4周,利用二氧化碳窒息处死实验小鼠,剖开胸腔后分离心脏组织,用于后续实验。H&E染色观察心脏组织结构;心室/体质量指数评估心室重构情况;荧光测定法测定心脏组织中组蛋白去乙酰化酶(HDACs)活性;qPCR检测MYH7、PDE4b、HDAC4、HDAC5及HDAC9的表达水平,Western blot检测PDE4b及HDAC9蛋白表达水平,ChIP-qPCR检测HDAC9与PDE4b启动子结合水平。结果与SHAM组相比,TAC组小鼠室间隔及左室壁明显增厚,心室/体质量指数明显升高(4.48±0.18 vs 5.50±0.23)(P<0.05),心肌肥厚标志物MYH7表达明显升高(0.91±0.04 vs 1.44±0.07)(P<0.05);PDE4b表达明显降低(mRNA水平0.75±0.09 vs 0.27±0.06;蛋白水平0.67±0.11 vs 0.34±0.05)(P<0.05);肥厚心肌组织中组蛋白去乙酰化酶活性显著增加(3.24±0.32 vs 5.03±0.58)(P<0.05),HDAC9表达显著升高(mRNA水平0.85±0.08 vs 1.35±0.07;蛋白水平0.77±0.10 vs 1.25±0.05)(P<0.05),而HDAC4、HDAC5表达与SHAM组无明显差异(P>0.05);HDAC9与PDE4b启动子结合水平明显升高(1.67±0.10 vs 2.47±0.20)(P<0.05)。结论心肌肥厚中HDAC9可能参与下调PDE4b表达,进而参与心室肌肥厚性重构。Objective To investigate the role of HDAC9 in regulating PDE4b in cardiac hypertrohpy.Methods 8-week old male c57 mice were treated with TAC surgery,Sham for mice of control group.6 weeks after TAC and Sham surgery,heart samples were collected.Cardiac general morphology was evaluated by H&E staining,heart weight/body weight ratio was calculated.Immunostaining was used for detecting activity of HDACs.Q-PCR was employed to determine expression levels of BNP,PDE4b,HDAC4,HADC5 and HDAC9.The protein levels of PDE4b and HDAC9 were detected by Western blot.ChIP-q-PCR was employed to analyze the binding status of HDAC9 with the promoter region of PDE4b.Results Heart ventricle and septum were significant hypertrophied.HW/BW was increased 4 weeks after TAC surgery(P<0.05).The expression levels of MYH7 and HDAC9 were increased compared with the controls(P<0.05).Total HDACs activity was enhanced in failure hearts(P<0.05).PDE4b levels reduced in mice of TAC surgery group(P<0.05).Binding affinity of HDAC9 with the promoter of PDE4b was reduced significantly(P<0.05).Conclusion HDAC9 regulating PDE4b low expression may cause cardiac hypertrophy remodeling.

关 键 词：心室肌重构 心肌肥厚 组蛋白去乙酰化酶9 磷酸二酯酶4b 

分 类 号：R542.2[医药卫生—心血管疾病]