Syndecan 4促进心肌细胞生理性肥大研究  

Syndecan 4 promotes cardiomyocyte physiological hypertrophy

作　　者：孙佳音[1] 周玉杰[1] 

机构地区：[1]首都医科大学附属北京安贞医院-北京市心肺血管疾病研究所12病房,100029

出　　处：《心肺血管病杂志》2016年第12期986-991,共6页Journal of Cardiovascular and Pulmonary Diseases

基　　金：北京市医院管理局"登峰"计划专项经费资助(DFL20150601)

摘　　要：目的:研究syndecan 4(Synd4)在心肌细胞生理性肥大中的作用及其机制。方法:将大鼠心肌细胞分为对照腺病毒组(Ad-lacz组),Synd4腺病毒转染组(Ad-synd4组),腺病毒+胰岛素样生长因子组(Ad-lacz+IGF组)和腺病毒+异丙肾上腺素组(Ad-lacz+ISO组),通过α-SMA染色观察细胞形态,S^(35)-半胱氨酸摄取试验检测蛋白质合成,real-time PCR检测胚胎基因和能量代谢相关基因表达,免疫印迹法测定caspase-3的表达。并在Ad-synd4转染的细胞中分别加入PKC阻滞剂Calphostin C和PI3K阻滞剂LY294002,α-SMA染色观察细胞形态,免疫印迹法测定Akt、p-Akt、PPARα的表达。结果:与IGF作用后相似,Synd4过表达可使细胞面积增大2倍,蛋白质合成增加50%,脂肪酸代谢相关基因PPARα和m CPT-1的mRNA表达明显上调(P<0.05),caspase-3蛋白的表达无变化。Calphostin C和LY294002均可抑制Synd4诱导的心肌细胞肥大和p-Akt、PPARα等蛋白的表达(P<0.05),但Calphostin C的作用更加明显。结论:Synd4可促进心肌细胞生理性肥大,其可能的作用机制是通过PKCα提高Akt磷酸化水平而实现的。Objective： To investigate the effects of syndecan 4（ Synd4） on cardiomyocyte physiological hypertrophy,and explore the potential underling mechanism. Methods： Cultured cardiomyocytes were randomly divided into four groups： control adenovirus group（ Ad-lacz group）,Synd4 group（ Ad-synd4 group）,adenovirus ＋ Insulin like growth factor group（ Ad-lacz ＋ IGF group） and adenovirus ＋ Isoprenaline group（ Ad-lacz ＋ISO group）. Cell size was observed by α-SMA-stained technique,protein synthesis was measured by S^（35）-methionine incorporation,the expression of fetal genes and energy metabolism related genes were detected by realtime PCR and the expression of caspase-3 was detected by western blot. Calphostin C and LY294002 was cotreated with Ad-synd4 in cardiomyocytes respectively,cell size was observed by α-SMA-stained technique and the expression of Akt、p-Akt、PPARα were detected by western blot. Results： As the effect of IGF,Synd4 over expression could induce cell enlargement,protein synthesis,and distinct physiological molecular alternation.Both Calphostin C and LY294002 could suppress cell enlargement and decrease the expression of p-Akt as well as PPARα induced by Synd4（ P〈0. 05）,but the effect of Calphostin C was more obvious. Conclusion： Synd4 could promote cardiomyocyte physiological hypertrophy. Its mechanism is in part,via increasing the phosphorylation of Akt via PKCα.

关 键 词：SYNDECAN 4 心肌细胞 生理性肥大 

分 类 号：R54[医药卫生—心血管疾病]