摘要
为研究血管再狭窄发生过程中 VSMC表型转化的规律及机制 ,采用大鼠主动脉内皮剥脱后血管再狭窄动物模型和体外培养的 VSMC,通过 Northern印迹分析及 3H- Td R参入实验 ,动态观察血管再狭窄发生过程中 VSMC表型标志基因α肌动蛋白和 SMemb的表达变化及 b FGF、TNF-α和 IL - 1β对两种基因表达的影响及其与 VSMC增殖之间的关系 .结果表明 ,血管内皮剥脱后 3d,分化型标志基因α肌动蛋白表达活性开始降低 ,去分化型标志基因 SMemb表达明显上调 ,至第 7d,前者的下调与后者的上调均达到最大 ,此后 ,两者的表达活性趋于向正常恢复 .b FGF可明显下调 α肌动蛋白的表达和诱导 SMemb表达 ,对分化型和去分化型 VSMC均有促增殖作用 ,但对后者的作用大于前者 ,TNF- α和 IL- 1 β对 VSMC的促转化及促增殖作用较弱 .提示 b FGF等生长因子介导血管内皮损伤所诱发的 VSMC表型转化并促进其增殖 ,内皮损伤 7d后 ,在发生表型转化并进行增殖的 VSMC中 ,一部分细胞再分化 ,一部分细胞仍处于去分化状态并继续进行增殖并持续较长时间 .
To study the regulation and mechanism on phenotypic switch of VSMC during vascular restenosis development,a rat model of vascular restenosis was established by balloon injury and cultured VSMCs were used.With Northern blotting and 3H TdR incorporation,the changes on VSMC phenotypic marker genes,α\|actin and SMemb expression during vascular restenosis development were observed,and the effects of basic fibroblast growth factor(bFGF),tumor necrosis factor\|α(TNF\|α)and interleukin\|1β(IL 1β) on the two gene expression,and the relation between these factors and VSMC proliferation were studied.The results showed that on day 3 after endothelial injury,the expression of differentiated phenotypic marker gene SM α actin was down\|regulated significantly,and dedifferentiated phenotypic marker gene SMemb was induced obviously.On day 7,these changes reached the peaks,then the two gene expression trended toward the normal level.bFGF could reduce α\|actin and induce SMemb expression,and could stimulate proliferation of differentiated and dedifferentiated VSMC,but the promotion on dedifferentiated VSMC was stronger.TNF\|α and IL 1β had less effects on VSMC phenotypic switch and proliferation.These results suggested that growth factors,such as bFGF,could stimulate VSMC phenotypic change and proliferation after vascular endothelial injury.On day 7,in the dedifferentiated and proliferated VSMCs,one part redifferentiated,and the other kept dedifferentiated and continued proliferating for a long time.
出处
《中国生物化学与分子生物学报》
CAS
CSCD
2000年第6期832-836,共5页
Chinese Journal of Biochemistry and Molecular Biology
基金
国家自然科学基金! (39970 2 74)
河北省自然科学基金! (3982 84)资助项目
关键词
球囊损伤
血管再狭窄
平滑肌细胞
表型转化
Balloon injury
Vascular restenosis
SMC
Phenotypic switch
Marker gene
SM α actin
SMemb
