摘要
目的：探讨ｃ－ｍｙｃ基因表达在血管平滑肌细胞增殖信号传导通路中的作用和采用反义ｃ－ｍｙｃ寡脱氧核苷酸抑制血管平滑肌细胞（ＳＭＣ）增殖的作用。方法：采用针对大鼠ｃ－ｍｙｃｍＲＮＡ包括ＡＵＧ在内的翻译起始区的前５个密码子的嵌合性硫代修饰的反义ｃ－ｍｙｃ寡脱氧核苷酸（ＡＳ－ＯＤＮ），以ｌｉｐｏｆｅｃｔｉｎ导入ＳＭＣ后，通过细胞计数和３Ｈ－ＴｄＲ掺入观察其对ＳＭＣ增殖的抑制作用。结果：ｃ－ｍｙｃＡＳ－ＯＤＮ不仅对从静止状态刺激的ＳＭＣ增殖有抑制作用，而且对处于增殖状态的ＳＭＣ的增殖也有显著抑制作用，这种抑制作用可因加入正义ｃ－ｍｙｃＯＤＮ而减弱甚至消除，而且随着剂量的增加，抑制作用越来越明显。一次性应用ｃ－ｍｙｃＡＳ－ＯＤＮ可达到较持久的作用。而正义ＯＤＮ和错配ＯＤＮ对ＳＭＣ增殖无影响。结论：ｃ－ｍｙｃＡＳ－ＯＤＮ以剂量依赖和序列特异方式抑制ＳＭＣ增殖。ｃ－ｍｙｃ基因表达在ＳＭＣ增殖的信号传导通路中起重要作用。为采用ｃ－ｍｙｃＡＳ－ＯＤＮ抑制ＳＭＣ增殖的反义战略防治再狭窄研究奠定了基础。
AIM:Investigate the role of c- myc gene expression in the signal transduction pathways mediating smooth muscle cell (SMC) proliferation and the effect of chimeric phosphorothioate antisense c- myc oligodeoxynucleotide (AS-ODN) on rat aortic SMC proliferation.METHODS:Chimeric phosphorothioate c- myc AS-ODN targeting the 1st 5 codons of translation initiation region of c- myc mRNA was introduced by lipofectin and its inhibitory effect on SMC proliferation was observed by cell count and -TdR incorporation. RESULTS:c- myc AS-ODN markedly suppressed proliferation of not only SMC stimulating from quiescent state but also exponential SMC. The inhibitory effect of c- myc AS-ODN on SMC proliferation was decreased and even abrogated by adding sense c- myc ODN. The larger dose there was, the greater inhibitory effect of c- myc AS-ODN on SMC proliferation there was. A single administration of c- myc AS-ODN had lasting action.Sense c- myc ODN and mismatch c- myc ODN had no significant effect on SMC proliferation compared with control. CONCLUSIONS:c- myc AS-ODN inhibited SMC proliferation in a dose-dependent and sequence-specific manner. This investigation indicates that c- myc gene product is involved in the signal transduction pathways mediating SMC proliferation and provides a basis for future study of the potential role of antisenese strategy using c- myc AS-ODN designed to inhibit SMC proliferation for the prevention of coronary restenosis
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
1999年第3期248-251,共4页
Chinese Journal of Pathophysiology
