曲古菌素A抑制血管平滑肌增殖和诱导凋亡的研究  

Effect of trichostatin A on proliferation and apoptosis of vascular smooth muscle cells

作　　者：邹琛[1] 吴春芳[1] 徐志红[1] 陆国平[1] 

机构地区：[1]上海交通大学附属瑞金医院心脏科,上海200025

出　　处：《中国药理学通报》2007年第12期1654-1657,共4页Chinese Pharmacological Bulletin

摘　　要：目的观察曲古菌素A(TrichostatinA,TSA)体外抑制血管平滑肌细胞(VSMC)增殖和诱导凋亡的作用。方法采用MTT比色法和BrdU参入法观察TSA对血清诱导的VSMC增殖的抑制作用;采用流式细胞仪和检测细胞周期蛋白表达的方法观察TSA对VSMC细胞周期的影响;采用测定DNA片段和活化caspase-3表达的方法观察TSA诱导VSMC发生凋亡的作用。结果小剂量TSA抑制血清诱导的VSMC增殖而无明显的细胞毒作用,大剂量TSA激活caspase-3并诱导VSMC发生凋亡。TSA干预可延缓血清诱导VSMC进入S期,此效应与抑制cyclinD1和cyclinA表达有关。结论TSA能抑制血清诱导的VSMC增殖,使VSMC停滞于静止期,大剂量条件下诱导VSMC凋亡。TSA有望成为治疗血管增殖性疾病的新策略。Aim To study the effect of TSA on vascular smooth muscle cells （VSMC） proliferation and apoptosis in vitro. Methods VSMC proliferation was analyzed by MTT assay and BrdU incorporation assay. Cell cycle phase distributions were determined by flow cytometer. The expressions of cyclin D1 and cyclin A were assessed by western blot. Cell apoptosis was quantified by detecting cytoplasmic histone-associated DNA-fragments and the level of cleaved caspase-3. Results TSA at a low concentration was adequate to inhibit serum-induced VSMC proliferation without significant cytotoxity. High concentration of TSA activated caspase-3 and induced VSMC apoptosis. TSA treatment reduced expressions of cyclin D1 and cyclin A, and blocked VSMC entry into S phase. Conclusions TSA inhibits serum-induced VSMC proliferation and G1→S phase progression of cell cycle. Histone deacetylase （HADC） inhibitors may constitute a novel therapy for vascular proliferative diseases.

关 键 词：曲古菌素A 血管平滑肌 细胞周期 凋亡 

分 类 号：R-332[医药卫生] R322.74