前列腺素E_1抑制血管平滑肌细胞增殖的作用

Effect of prostaglandin E_1 against proliferation of vascular smooth muscle cells

目的 从细胞周期蛋白和凋亡相关基因探讨前列腺素E1(PGE1)对血管平滑肌细胞 (VSMC)增殖的调控作用。方法 采用培养的新生牛主动脉VSMC ,以胎牛血清及白介素 1(IL 1)分别作为促增殖剂 ,测定不同浓度PGE1对VSMC增殖、细胞内周期蛋白d1mRNA表达、p5 3及Bcl 2基因表达和培养液内NO含量的影响。结果 PGE1浓度依赖性抑制胎牛血清促VSMC增殖作用 ;显著减少细胞周期蛋白d1mRNA含量 ;浓度依赖性诱导IL 1孵育下VSMC产生大量NO ,同时抑制VSMC增殖 ;并促进p5 3基因表达 ,下调bcl 2基因 ,诱导细胞凋亡。结论 PGE1具有抑制VSMC增殖的作用 ,其机制可能与其阻滞VSMC生长有关 ;在炎性因子存在情况下 ,PGE1可诱导VSMC内大量产生NO ,抑制VSMC增殖 ,并加速VSMC凋亡。

AIM To investigate the regulatory action of prostaglandin E 1(PGE 1) on proliferation of vascular smooth muscle cells (VSMC) in respect to cyclin and apoptosis related genes. METHODS Fetal calf serum (FCS) or interleukin (IL 1) were used as proliferation promoter. Cultured VSMC from neonatal bovine aorta were assayed for cyclin d1 mRNA, expression of p53 and bcl 2 genes, and the content of NO after being treated with three doses of PGE 1. RESULTS PGE 1 dose dependently inhibited proliferation of VSMC induced by FCS,decreased the amount of cyclin d1 mRNA; PGE 1 dose dependently induced NO production, increased p53 gene expression while depressing Bcl 2 gene expression of VSMC incubated with IL 1. PGE 1 could induce VSMC apoptosis. CONCLUSION PGE 1 inhibits VSMC proliferation. The mechanism is probably related to the decrease in the cyclin d1 mRNA amount and arrests the cell growth. With the existence of IL 1, PGE 1 induces the production of large amount of NO in VSMC, inhibits VSMC proliferation and accelerates VSMC apoptosis.