p15与c-Myc在TGF-β1诱导的大鼠心肌细胞肥大中的表达及与TGF/Smad信号通路的关系  

Study on p15 and c-Myc with TGF/Smad signal pathway of cardiomyocyte hypertrophy induced by TGF-β1 in rat

作　　者：石永英[1] 卢俊江 陈广原[3] 刘世明[4] 陈敏生[5] SHI Yong-Ying;LU Jun-Jiang;CHEN Guang-Yuan;LIU Shi-Ming;CHEN Min-Sheng(Department of Geriatrics, the First Affiliated Hospital of Guangzhou Medical University ＆ Guangzhou Institute of Cardio- vascular Disease, Guangzhou, Guangdong 510120, China;Department of Neurology, Guangzhou Chest Hospital, Guang- zhou, Guangdong 510095, China;Department of Geriatrics, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510120, China;Department of Cardiology, the Second Affiliated Hospital of Guangzhou Medical University ＆ Institute of Cardiovascular Disease, Guangzhou, Guangdong 510260, China;1nstitute of Cardiovascular Dis- ease, Zhujiang Hospital, Southern Medical University, Guangzhou , Guangdong 510515, China)

机构地区：[1]广州医科大学附属第一医院老年科广州心血管病研究所,广东省广州市510120 [2]广州胸科医院神经内科,广东省广州市510095 [3]广州医科大学附属第一医院老年科,广东省广州市510120 [4]广州医科大学附属第二医院心内科广州心血管病研究所,广东省广州市510260 [5]南方医科大学附属珠江医院心血管病实验室,广东省广州市510515

出　　处：《中国动脉硬化杂志》2018年第3期245-252,共8页Chinese Journal of Arteriosclerosis

基　　金：广东省医学科学技术研究基金项目(A2016376)

摘　　要：目的探讨转化生长因子β1（TGF-β1）诱导的大鼠心肌细胞肥大中Smad信号通路及其目的蛋白p15的表达。方法建立TGF-β1诱导的体外大鼠心肌细胞肥大模型。PI染色标记细胞双链RNA法检测心肌细胞RNA表达量,间接检测心肌细胞肥大。实时荧光定量PCR检测心肌细胞肥大相关基因β肌球蛋白重链（β-MHC）的表达。Smad2 siRNA干扰Smad信号通路表达并检测其相关蛋白表达。Western blot检测心肌细胞p-Smad2、Smad2、Smad2/3、p15及c-Myc蛋白表达。结果 TGF-β1可诱导体外培养的心肌细胞肥大基因的表达,β-MHC的表达明显高于对照组（P〈0.01）。PI染色标记细胞双链RNA法检测发现,TGF-β1组RNA含量明显增高（P〈0.01）,与对照组相比,TGF-β1可明显上调p-Smad2、Smad2、Smad2/3及Smad通路目的蛋白p15、c-Myc的表达（P〈0.01）。给予Smad2 siRNA特异性干扰后,p15表达较TGF-β1组减少（P〈0.01）。结论 TGF-β1可能通过Smad蛋白通路诱导心肌细胞肥大形成,此过程中相关目的蛋白p15表达增加。Aim To investigate pathway mechanism about transforming growth factor-β1（ TGF-β1） activated cardiomyocyte hypertrophy. Methods Fresh isolated neonatal rat cardiomyocytes induced by TGF-β1 were used to examine formation of cell pathway. p-Smad2,Smad2,Smad2/3,p15 and c-Myc proteins were measured by Western blot.Cardiomyocyte hypertrophy was measured by PI statining and RNA expressions by real-time PCR. Smad signal pathway expression and it＇s related protein expression were induced by TGF-β1 and siRNA interference. Results TGF-β1 could induce the expression of hypertrophic gene in cultured cardiomyocytes in vitro,and the expression of β-MHC was significantly higher than that of the control group（ P〈0.01）. The content of RNA in TGF-β1 group was significantly increased by PI staining（ P〈0.01）. Compared with the control group,TGF-β1 significantly increased the expression of p15 and c-Myc in p-Smad2,Smad2,Smad2/3 and Smad pathway（ P〈0.01）. The expression of p15 of Smad2 siRNA group was less than that of TGF-β1 group（ P〈0.01）. Conclusion TGF-β1 may induce cardiomyocyte hypertrophy through the Smad protein pathway,and in this process the expression of p15 is increased.

关 键 词：转化生长因子β1 心肌细胞肥大 TGF/Smad信号通路 P15 C-MYC 

分 类 号：R363[医药卫生—病理学]