局部应用没食子儿茶素-3-没食子酸抑制移植静脉内膜增生
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Locally Delivered Epigallocatechin-3-Gallate Inhibiting Intimal Hyperplasia in a Model of Vein Bypass Grafting
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    摘要:

    目的探讨局部应用没食子儿茶素-3-没食子酸对移植静脉内膜增生的抑制作用及其发生机制。方法应用异硫氰酸荧光素荧光标记技术和高效液相色谱法体外定性和定量测定血管对没食子儿茶素-3-没食子酸的吸收情况。日本大耳白兔20只,随机分为没食子儿茶素-3-没食子酸处理组和对照组(n=10)。建立兔颈外静脉与颈内动脉间置移植模型,移植前没食子儿茶素-3-没食子酸处理组血管在0.1 g/L没食子儿茶素-3-没食子酸中常温保存1 h,而对照组血管保存在生理盐水中。组织学方法测定移植三周后移植静脉血管新生内膜厚度、内膜中膜厚度比,原位DNA断裂位点的3′-羟基末端标记、Ki67免疫组织化学染色测定新生内膜阳性细胞百分比。结果0.1g/L没食子儿茶素-3-没食子酸中保存1 h2、h4、h,静脉血管的吸收量分别为2.9±0.9 mg/g、5.8±2.1 mg/g和8.0±2.3 mg/g,分布在血管壁全层。两组移植血管术后3周的通畅率均为90%(9/10)。移植术后3周没食子儿茶素-3-没食子酸处理组较对照组内膜厚度(41.1±13.6μm比89.9±48.3μm,p<0.01)及内膜/中膜厚度比(0.40±0.18比0.77±0.31,p<0.05)均显著降低,新生内膜Ki67阳性染色平滑肌细胞百分比也显著下降(22.4%±8.6%比8.8%±2.4%,p<0.05),而凋亡细胞百分比(0.40%±0.55%比0.60%±0.89%,p>0.05)无明显变化。结论局部应用没食子儿茶素-3-没食子酸能够抑制移植静脉内膜增生,可能与其抑制内膜平滑肌细胞增殖有关。

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    Aim To examine the effect of epigallocatechin-3-gallate(EGCG) on intimal hyperplasia in a vein graft model by local delivery. Methods Rabbit jugular vein segments were incubated in saline containing EGCG 0.1 g/L.HPLC and FITC-labelled EGCG were used to assess the absorption characteristics of EGCG in vitro.Autogenous vein graft model was established in 20 rabbits which were randomly divided into two groups: EGCG group and control group.Vein grafts were incubated with EGCG or saline before arterial interposition grafting(n=10).Animals were sacrificed 21 days later and intimal thickening(intimal thickness and intimalto-medial ratio,I and I/M) was assessed by computerized digital morphometry.The proliferation and apoptosis of neointimal cells were determined by Ki67 staining and terminal deoxynucleotidyl transferase biotin nick end-labeling(TUNEL) method,respectively. Results At dose of 0.1 mg/L,the vein segments showed evidence of EGCG localization,EGCG was absorbed at levels of 2.9±0.9 mg/g,5.8±2.1 mg/g and 8.0±2.3 mg/g after incubation for 1 h,2 h and 4 h,respectively.All animals survived until the time of harvest,and there was 1 closed case respectively in two study groups.The EGCG group showed a significant reduction in neointimal formation at 21 days compared with the control condition(41.1±13.6 μm vs 89.9±48.3 μm,p<0.01 and 0.40±0.18 vs 0.77±0.31,p<0.05).Immunohistochemical analysis of Ki67 also indicated decreased rate of positive smooth muscle cells in the EGCG group(22.4%±8.6% vs 8.8%±(2.4%),p<0.05).Cell apoptosis was not different in two groups(0.40%±0.55% vs 0.60%±0.89%,p>0.05). Conclusions These results indicate that the local delivery of EGCG prevent intimal hyperplasia in a rabbit vein bypass grafting model through inhibition of neointimal smooth muscle cells proliferation.

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姜春力,谷天祥.局部应用没食子儿茶素-3-没食子酸抑制移植静脉内膜增生[J].中国动脉硬化杂志,2005,13(6):741~743.

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  • 收稿日期:2005-02-26
  • 最后修改日期:2005-11-20
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