表没食子儿茶素-3-没食子酸(EGCG)对大鼠自体移植静脉桥狭窄的抑制作用及其机制研究  

Inhibitory effect and mechanism of epigallocatechin-3-gallate on autogenous vein graft stenosis in rat models

作　　者：张毅[1] 古君[2] 刘林波[1] 廖智杰[1] 张洪伟[2] 杨鹏[2] 范康钧 梁怀民[2] 肖正华[2] 胡佳[2] 

机构地区：[1]绵阳市第三人民医院普外血管外科,四川绵阳621000 [2]四川大学华西医院心脏大血管外科,成都610041

出　　处：《中国胸心血管外科临床杂志》2017年第10期791-796,共6页Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

基　　金：国家自然科学青年基金项目(81300155);国家自然科学基金项目(81670327)

摘　　要：目的探讨表没食子儿茶素-3-没食子酸(EGCG)对大鼠自体静脉移植再狭窄的抑制作用及其相关机制。方法 90只雄性Sprague-Dawley(SD)大鼠,随机分为对照组、实验组(自体静脉移植组)和EGCG干预组(自体静脉移植+EGCG干预组),术后1、2和4周通过病理切片检测各组颈外静脉内膜、中膜厚度,免疫组化检测颈外静脉中反映平滑肌细胞增殖的Ki-67表达情况,通过蛋白质免疫印迹法(Western blot)检测颈外静脉中转录因子发状分裂相关增强子1(HES1)蛋白表达情况。结果第2周实验组与对照组和EGCG干预组相比,颈外静脉内膜[(46.76±4.89)μm vs.(8.93±0.82)μm,(46.76±4.89)μm vs.(34.24±3.57)μm]、中膜厚度[(47.28±4.37)μm vs.(16.33±1.52)μm,(47.28±4.37)μm vs.(36.27±3.29)μm],Ki-67阳性率(21.59%±2.29%vs.1.12%±0.22%,21.59%±2.29%vs.15.38%±1.30%)和HES1蛋白表达均显著增加(P<0.05)。第4周实验组与对照组和EGCG干预组相比,颈外静脉内膜[(66.38±6.23)μm vs.(8.29±0.79)μm,(66.38±6.23)μm vs.(48.39±4.23)μm]、中膜厚度[(63.27±6.18)μm vs.(15.29±1.49)μm,(63.27±6.18)μm vs.(44.63±4.49)μm],Ki-67阳性率(33.19%±3.03%vs.1.09%±0.19%,33.19%±3.03%vs.24.37%±2.73%)和HES1蛋白表达也显著增加(P<0.05)。结论 EGCG可能通过抑制Notch通路发挥保护自体静脉桥移植后再狭窄作用。Objective To investigate the effect and mechanism ofepigallocatechin-3-gallate （EGCG） on restenosis of the vein graft. Methods Totally 90 Sprague-Dawley rats were randomly divided a the control group, a vein graft group and an EGCG＋vein graft group. At week 1, 2 and 4, the intimal and tunica thickness of the venous graft wall was evaluated by hematoxylin-eosin staining, and the expression of Ki-67 was assessed by immunohistochemistry analysis, and then the expression of hairy and enhancer of split-1 （HES1） was measured by Western blot assay. Results At week 2, the intimal thickness （46.76±4.89μm vs. 8.93±0.82 μm, 46.76±4.89 [am vs. 34.24±3.57μm）, tunica thickness （47.28±4.37 vs. 16.33±1.52μm, 47.28±4.37 vs. 36.27±3.29 μm）, positive cell rate of Ki-67 （21.59%±2.29% vs. 1.12%±0.22%, 21.59%±2.29% vs. 15.38%±1.30%）, expression of HES1 respectively increased in the experimental group than those in the control group and the EGCG＋vein graft group （P〈0.05, respectively）. At week 4, the intimal thickness （66.38±6.23μm vs. 8.29±0.79 μm, 66.38±6.23 μm vs. 48.39±4.23μm）, tunica thickness （63.27±6.18μm vs. 15.29±1.49μm, 63.27±6.18 μm vs. 44.63±4.49μm）, positive cell rate of Ki-67 （33.19%±3.03% vs. 1.09%±0.19%, 33.19%±3.03% vs. 24.37%±2.73%）, expression of HES1 increased in the experimental group than those in the control group and EGCG＋vein graft group （P〈0.05, respectively）. Conclusion EGCG may inhibite restenosis of vein graft by inhibiting Notch signal pathway.

关 键 词：自体静脉移植 表没食子儿茶素-3-没食子酸 NOTCH通路 转录因子发状分裂相关增强子1 

分 类 号：R654.3[医药卫生—外科学]