不同端粒片段通过沉默信息调节因子1/抑癌基因P53促进血管平滑肌细胞凋亡  

Different Telomere Fragments Promote Rat's Vascular Smooth Muscle Cell Apoptosis by Silent Information Regulator 1/Cancer Suppressor Gene P53

作　　者：吕娟[1] 王红[1] 

机构地区：[1]成都军区昆明总医院高干病房,云南省昆明市650031

出　　处：《中国循环杂志》2017年第6期612-616,共5页Chinese Circulation Journal

基　　金：国家自然科学基金(81270224)

摘　　要：目的:研究不同端粒寡核苷酸序列对大鼠胸大动脉平滑肌细胞(A7R5)凋亡的影响,及沉默信息调节因子1(SIRT1)/抑癌基因P53(P53)信号通路是否参与调控端粒寡核苷酸序列诱导A7R5的凋亡。方法:将三种端粒重复序列端粒寡核苷酸序列的二聚体、四聚体、六聚体[TE-12(TTAGGG)2、TE-24(TTAGGG)4、TE-36(TTAGGG)6]转染至A7R5,分别作为TE-12组、TE-24组、TE-36组,另设A7R5空白为阴性对照组。应用流式细胞仪检测各端粒寡核苷酸序列转染后A7R5的凋亡情况。采用逆转录多聚酶联反应(RT-PCR)及蛋白免疫印迹(Western-blot)检测TE-12组、TE-24组、TE-36组及阴性对照组SIRT1、P53基因及蛋白水平。结果:将TE-12、TE-24、TE-36成功转染进A7R5,各组转染率差异无统计学意义。TE-12组A7R5凋亡率明显高于TE-36组、TE-24组和阴性对照组,TE-24组细胞凋亡率最低,但亦明显高于阴性对照组,差异均有统计学意义(P均<0.05)。TE-12组A7R5SIRT1m RNA及蛋白水平明显高于TE-36组、TE-24组和阴性对照组,差异均有统计学意义(P均<0.05)。TE-24组A7R5P53m RNA及蛋白水平明显低于TE-36组、TE-12组和阴性对照组,差异均有统计学意义(P均<0.05)。结论:端粒寡核苷酸序列促进A7R5的凋亡。不同结构的端粒寡核苷酸序列引起A7R5凋亡程度不同,在选取的三种结构中,端粒单链序列TE-12引起A7R5凋亡最明显。端粒寡核苷酸序列对A7R5凋亡的作用可能与SIRT1/P53信号通路有关。Objective： To study the influence of different telomere oligonucleotide on rat＇s thoracic aortic smooth muscle （A7R5 ） cell apoptosis and to clarify weather silent information regulator 1 （SIRT1）/cancer suppressor gene （P53） signaling pathway involved in oligonucleotide induced cell apoptosis. Methods： 3 telomere repeat sequences of TE-12 （TTAGGG）2, TE-24 （TTAGGG）4 and TE-36 （TTAGGG）6 were respectively transfected into rat＇s A7R5 cells as TE-12 group, TE-24 group and TE-36 group; in addition, blank A7R5 cells were used as Control group. Transfection induced A7R5 cell apoptosis was detected by flow cytometry, mRNA and protein expressions of SIRT1 and P53 in A7R5 cells were examined by RT-PCR and Western blot analysis in different groups. Results： Successful ransfection rates were similar among 3 groups. Compared with Control group and TE-36, TE-24 groups, the highest apoptosis rate of A7R5 cells was found in TE-12 group and the lowest was found in TE-24 group which was still higher than that in Control group, allP〈0.05. mRNA and protein expressions of SIRT1 was obviously higher in＆nbsp;TE-12 group than the other 3 groups, allP〈0.05; mRNA and protein expressions of P53 was obviously lower in TE-24 group than the other 3 groups, allP〈0.05. Conclusion： Telomere oligonucleotide sequence may promote rat＇s A7R5 cell apoptosis; different sequence had various influence and the strongest effect was observed in TE-12 sequence. The above impact might be related to SIRT1/P53 signaling pathway.

关 键 词：寡核苷酸类 肌 平滑 血管 凋亡 

分 类 号：R54[医药卫生—心血管疾病]