STAT3信号通路与血管重塑中平滑肌细胞表型转化及增殖关系  

STAT3 signaling pathway and its relationship with phenotypic modulation and proliferation of vascular smooth muscle cells in vascular remodeling

作　　者：邱志兵[1] 陈鑫[1] 万松[2] 叶辉贤[2] 翟志成[2] 

机构地区：[1]南京医科大学附属南京第一医院南京市心血管病研究所心胸外科,210006 [2]香港中文大学威尔斯亲王医院心胸外科

出　　处：《中华实验外科杂志》2008年第12期1624-1626,共3页Chinese Journal of Experimental Surgery

摘　　要：目的观察静脉桥再狭窄模型中血管平滑肌细胞（VSMC）表型转化和增殖活性的变化，探讨信号转导子和激活子3蛋白（STA33）的表达与VSMC表型转化及增殖活性的关系。方法建立猪静脉桥再狭窄模型，采用血管病理形态学、免疫组织化学和免疫印迹（Western blot）方法，观察术后7、14、30d血管重塑及血管壁中增殖细胞核抗原（PCNA）、平滑肌α肌动蛋白（SM-α-actin）和STAT3表达变化及其相关性。结果（1）术后7d新生内膜形成逐渐增厚，于术后30d达最大；重塑指数和外弹力板围绕面积（EELA）术后7d稍有增大，其后不断减小，术后14—30d明显减小（P〈0．05）。（2）免疫组织化学和Western blot测定STA33蛋白显示，术后7d中膜VSMC中阳性表达明显，术后14d中膜VSMC和内膜VSMC中阳性表达均增加达高峰；术后30d中膜VSMC中有较少部分阳性表达，内膜VSMC中阳性表达较14d减少。血管中膜中STAT3和PCNA的蛋白呈显著性正相关（r=0．726，P〈0．05）。结论血管平滑肌细胞的表型转化和增殖活性改变对内膜增生和血管重塑起着重要作用，STA33信号通路与血管重塑中VSMC的增殖高度相关，参与并促进了VSMC的表型转化和增殖。Objective To investigate the phenotypic modulation and proliferation changes of vascular smooth muscle cells （VSMCs） in the vein graft restenosis model. To evaluate the expression of signal transducer and activator of transcription 3 （STAT3） and its relationship with the phenotypic modulation and proliferation changes of VSMCs in vascular remodeling. Methods The pig autogenous vein grafts restenosis model was created. Specimens were harvested at 3 time points of 7th, 14th and 30th day. Histomorphometrical ,immunohistochemical and immunofluorescence methods were used to detect the changes of vascular remodeling, the expression and relationship of proliferation cell nuclear （PCNA） , smooth muscle- α-actin （SM-α-actin） and STAT3. Results （ 1 ） At 7th day after operation, the neointima was continuously thickened, and reached the peak on the postoperative day 30. Although remodeling index and the thickness of EELA were slightly increased at day 7 after operation, they were markedly increased on the postoperative day 14 and 30 as compared with day 7 （P 〈0. 05）. （2） Immunostaining and Western blot showed that the positive STAT3 expression of VSMCs was significant in the medium at 7th day after operation, and the area of positive expression of VSMCs in the neointima and medium reached peak at day 14 （ P 〈 0.05 ）. At 30th day, only focal and mild STAT3 expression was detected in the media, and the positive expression of VSMCs in the neointima was decreased significantly as compared with 14th day （ P 〈 0.05 ）. The expression of STAT3 in VSMCs in the media region showed a marked positive correlation with the expression of PCNA （ r = 0.726,P 〈 0.05 ）. Conclusion The phenotypic modulation and proliferation changes of vascular smooth muscle cells are the important factors on intimal hyperplasia and vascular remodeling. There is a significant correlation between the expression of STAT3 and the proliferation of VSMCs. Signal pathway of STAT3 is involved and accelerated in the phe

关 键 词：信号转导子和激活子3 血管平滑肌细胞 增殖 血管重塑 

分 类 号：R654.2[医药卫生—外科学]