颈总动脉压诱导的小鼠移植静脉血管重构  

Mouse Venous Bypass Graft Remodeling Induced by Carotid Blood Pressure

作　　者：李宇煌[1] 张征宇[1] 汪照静[1] 刘树迎[1] 陈大堤[1] 黄锦桃[1] 胡黎平[1] 李朝红[1] 

机构地区：[1]中山大学中山医学院组织学与胚胎学教研室,广东广州510089

出　　处：《中山大学学报（医学科学版）》2011年第2期175-181,共7页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：国家自然科学基金(30570762;30871023;81070124);广东省自然科学基金(8151008901000044);高等学校博士学科点专项科研基金(20090171110049)

摘　　要：【目的】研究血压升高引起血管重构的机制。【方法】手术取出麻醉后的11～12周供体C57BL/6J小鼠的下腔静脉,连接到同窝出生的受体小鼠颈总动脉,构建"静脉桥"。继而,收获受颈总动脉压作用不同时间(0,2,4,8周)后的移植静脉,经石蜡包埋HE染色、丽春红-维多利亚蓝染色以及平滑肌特异性抗体免疫组化染色后观察其血管构筑。【结果】术后各时间点均可见移植静脉血管壁增厚及新生内膜的形成,呈时间依赖性。与正常静脉[(11.10±0.9)μm)]相比,术后8周血管壁[(88.97±16)μm)]增厚了8倍(P<0.01)。术后2周移植静脉新生内膜中即可见血管平滑肌细胞大量增生,4周最多,8周后数量减少,但细胞外基质明显增多。移植静脉在动脉压作用下,其弹性膜历经了断裂、合成和重建过程。【结论】血压升高产生的机械力可直接导诱导移植的小鼠静脉粥样硬化以及弹力膜的重构。本研究可望为深一步探索高血压引起血管重构的机制及防治新策略提供有用的动物模型及实验依据。[Objective] To establish a venous bypass graft arteriosclerotic mouse model for exploring the mechanisms of vascular remodeling induced by blood pressure-related mechanical stress.[Methods] The right common carotid arteries of anesthetic 11-12 week-old C57BL/6J mice were cut in the middle,and polyethylene cuffs were placed at both ends of the arteries.Then the supradiaphragmatic vena cava from isogenic littermate donor mice were harvested and grafted as interposition grafts.Morphometric assessments including HE staining,Ponceau-Vitoria-blue staining and immunohistochemistry were performed on paraffin-embeded sections of the vein grafts harvested 2 weeks,4 weeks,8 weeks after surgery.[Results] The grafted veins in response to carotid artery pressure demonstrated remarkably increased vessel wall thickness in a time-dependent manner.The neointima of the veins grafted 8 w increased about 8 folds than that of normal vein control[（88.97 ± 16） μm vs（11.10 ± 0.9）μm,P 0.01）].Furthermore,significant proliferation of vascular smooth muscle cells（α-actin＋） could be seen in the neointimal lesions increasing at 2 weeks postsurgery,reaching peak at 4 weeks and then decreasing at 8 weeks with increased extracellular matrix.In addition,the elastic membranes of the grafted veins underwent fragmentation,synthesis and reorganization from 2 weeks to 8 weeks after grafting.[Conclusions] Increased blood pressure-initiated mechanical stress can directly induce mouse venous bypass graft artherosclerosis and elastic membrane remodeling.The study would provide a novel animal model for exploring molecular mechanisms of vascular remodeling and prevention and treatment of hypertension.

关 键 词：高血压 血管重构 血管平滑肌细胞 弹力膜 

分 类 号：R363[医药卫生—病理学]