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张保亭,颜乾麟,颜德馨,李智,于永春,黄国平,汤德生,叶新.稳斑护脉颗粒对动脉粥样硬化斑块稳定性影响的分子机制[J].,2005,(2):154-159
稳斑护脉颗粒对动脉粥样硬化斑块稳定性影响的分子机制
Molecular Mechanism of Effect of Wenban Humai Granule on Stability of Atheromatous Plaque
  
DOI:
中文关键词:  稳斑护脉颗粒  辛伐他汀  斑块稳定  胶原纤维  家兔  中药
英文关键词:Wenban Humei granule  simvastatin  plaque stabilization  collagen  rabbit  Chinese herbs
基金项目:上海市卫生局资助项目(No2002J007B)
Author NameAffiliation
ZHANG Baoting 同济大学附属上海市第十人民医院中医科 
YAN Qian-lin 同济大学附属上海市第十人民医院中医科 
YAN De-xin 同济大学附属上海市第十人民医院中医科 
李智 同济大学附属上海市第十人民医院中医科 
于永春 同济大学附属上海市第十人民医院中医科 
黄国平 同济大学附属上海市第十人民医院中医科 
汤德生 上海第二医科大学药理教研室 
叶新 同济大学医学院药理教研室 
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中文摘要:
      目的 研究稳斑护脉颗粒稳定动脉粥样硬化斑块的分子机制,观察其对动脉粥样斑块纤维帽中胶原纤维降解与合成失衡状态的影响。方法 采用高脂饮食的家兔动脉粥样硬化模型,以免疫组织化学染色、原位杂交方法,检测造模前后和服药前后动脉粥样硬化家免新生内膜中巨噬细胞CD68、基质金属蛋白酶-1(MMP-1)、平滑肌细胞α肌动蛋白(SMC-α-actin)和Ⅰ型胶原(Collagen Type Ⅰ)蛋白、mRNA表达水平的变化。结果 家兔高脂饮食7周后,主动脉新生内膜中巨噬细胞CD68蛋白、MMP-1蛋白和mRNA表达水平显著上升,同时,主动脉中膜的平滑肌细胞迁移至新生内膜导致新生内膜中的SMC-α-actin蛋白、CollagenType Ⅰ蛋白和mRNA水平略有上升。服用稳斑护脉颗粒和辛伐他汀8周后,家兔主动脉新生内膜中巨噬细胞CD68蛋白、MMP-1蛋白和mRNA表达水平明显回落(P<0.01),同时,稳斑护脉颗粒组新生内膜中SMC-α-actin蛋白、Collagen Type Ⅰ蛋白和mRNA表达进一步增加(P<0.01),而辛伐他汀组家兔主动脉新生内膜中SMC-α-actin蛋白、Collagen Type Ⅰ蛋白和mRNA表达呈下降趋势(分别P>0.05,P<0.05),整个过程中,家兔主动脉新生内膜巨噬细胞CD68和MMP-1蛋白表达以及SMC-α-actin和Collagen Type Ⅰ蛋白表达的变化均呈正相关(分别为r=0.952,P<0.01;r=0.79
英文摘要:
      To explore the molecular mechanism of Wenban Humai granule (WHG) in stabilizing athero matous plaque, by observing its effect on the collagen degradation and synthesis imbalance manner in the fibrous cap of the plaque. Methods Atherosclerosis (AS) rabbit model established by feeding high fat diet. The changes of protein and mRNA expression of macrophage CD68, metalloproteinase-1 (MMP-1), α-smooth muscle actin (α-SMA) and collagen Ⅰ (C-Ⅰ) in model rabbits’ neo-genesic intima were determined by immunohis tochemical stain and in situ hybridization methods before and after treatment as well as before and after modeling. Results After being fed with high fat diet for 7 weeks, the protein and mRNA expression of macrophage CD68, MMP-1 in neo-genesic intima of aorta in the model rabbits significantly increased, these changes could be significantly restored after 8 weeks treatment with WHG or simvastatin. At the same time, the expressions of α-SMA protein and C-Ⅰprotein and mRNA slightly increased due to the immigration of SMC in aortic media to neo-genesic intima, these expressions could be further increased after WHG treatment but showed a reducing trend after simvastatin treatment (P<0.05 and P<0.01). In the whole course, positive correlation was shown between protein expressions of CD68 and MMP-1 (r = 0.952, P<0.01) and also between these of α-SMA and C-Ⅰ( r = 0 .793, P < 0.01). Conclusion WHG affects the collagen degradation and synthesis imbalance in the fibrous cap of the plaque to stabilize plaque through bi-directional regulation, up-regulating synthesisthesis factors and down-regulating degradation factors, while simvastatin perform its action on plaque stability by down-regulating degradation factors alone.
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