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PDGFR-β反义寡核苷酸防治血管再狭窄的作用机制(PDF)

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2002年第2期
页码:
110-112,115
栏目:
实验研究
出版日期:
2002-03-01

文章信息/Info

Title:
The mechanism of PDGFR-β antisense oligonucleotide for prevention of vessel restenosis in vitro
作者:
侯英萍;  顾春虎;  乔宏庆;  邓敬兰
第四军医大学西京医院核医学科, 陕西 西安 710032
Author(s):
HOU Ying-ping ;  GU Chuen-hu;  QIAO Hong-qing ;  DENG Jing-lan
Department of Nuclear Medicine, Xijing Hospital, Fourthb Military Medical University, Xi’an,Shaanxi 710032, China
关键词:
血管平滑肌细胞;  血管再狭窄;  血小板衍化生长因子;  反义寡核苷酸
Keywords:
vascular smooth muscle cell;  vessel restenosis;  platelet-derived growth factor-Breceptor;  antisense oligonucleotide
分类号:
R322.1+ 2
DOI:
-
文献标识码:
A
摘要:
目的 观察血小板衍化生长因子-β受体（PDGFR－β）反义寡核苷酸（AODN）对血管平滑肌细胞（VSMC）的增殖，迁移，凋亡和细胞周期的影响以及AODN的摄取和细胞内定位，以期从细胞和分子水平上探讨其防治血管再狭窄的作用机制。方法 建立大鼠胸主动脉VSMC体外增殖模型，实验选用5－10代VSMC并将之分为4组；空白组，反义组，正义组及错义组。改良的Boyden‘s小室观察细胞迁移；MTT比色法测定细胞增殖活力；TUNEL及流式细胞仪观察细胞凋亡及周期；激光共聚焦显微镜观察FITC标记ACDN摄取及细胞内定位。结果 （1）反义组对VSMC的增殖和迁移抑制作用均高于空白，正义及错义组（P＜0．05）。（2）AODN干预后48h ,TUNEL染色呈阳性结果，且凋亡率为30．8％，而空白组仅为10．3％，两组间有显著性差异（P0．05）;(3)反义组细胞G1期数量明显增加；（4）加药后24h AODN位于胞浆内，48h位于胞核内。结论 PDGFR－β反义寡核苷酸可抑制体外VSMC增殖和迁移，使VSMC停留于G1期，并促进细胞凋亡，初步阐明了PDGFR－β反义寡核苷酸防治血管再狭窄的作用机制。
Abstract:
AIM To observe the effect of platelet-derived growth factor-β receptor (PDGFR-β) antisense oligonucleotide on proliferation, migration, apoptosis , cell cycle progression of cultured rat vascular smooth muscle cells (VSMC) and up take and localization of antisen seoligonucleotide in VSMC, and explore the mechanism of PDGFR-β antisense oligonucleotide in preventing the restenosis at cellular and molecular level. METHODS Cultured rat aortic VSMC proliferation model was established in vitro. Cells of 5～ 10 passages were used in experiment, which was divided in to four groups: control, antisense oligonucleotide (AODN ) , sense oligonucleo tide(SODN ) and scram bled oligonucleotide (SCODN ). Modified boyden’s chambers was used to observe VSMC migration. VSMC proliferation viability was determined by MTT assay. Cell apoptosis and cell cycle were performed with TUNEL and Flow cytometry. The up take and localization of FITC-labeled AODN were detected by laser confocal microscopy. RESULTS ①The inhibition of cultured VSMC proliferation and migration in AODN group was significantly stronger than that of control, SODN and SCODN groups; ②After incubated with AODN 48 h, VSMC stained by TUNEL was positive. The percen tage of TUNEL positive cell in AODN group (30.8% ) was significantly higher as compared to control group (10. 3%) (P0. 01) ; ③The number of cell of G1 phase in AODN group was remarkably increased; ④The fluorescence was localized primarily in cytoplasm at 24 h, whereas in cell nuclei at 48 h. CONCLUSION PDGFR-β AODN could suppress proliferation and migration VSMC, arrest cell in G1 phase and induce VSMC apoptosis in vitro. The mechanism of PDGFR-β AODN could be preliminarily clarified for prevention of vessel restenosis.

参考文献/References

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备注/Memo

备注/Memo:
收稿日期：2001-10-09.基金项目: 全军医药卫生科研基金资助项目(No：01MA194)　
更新日期/Last Update: 2002-03-01