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

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兔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(CollagerlTypeⅠ)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、Collagen TypeⅠ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 TypeⅠ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、collageil TycpeⅠ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 TypeⅠ蛋白表达的变化均呈正相关(分别为r=0．952，P<0．01；r=0．793，P<0．01)。结论 稳斑护脉颗粒通过上调纤维帽合成因素与下调纤维帽降解因素的双向靶标，而辛伐他汀通过下调纤维帽降解因素的单向靶标，来影响动脉粥样硬化家兔斑块纤维帽中胶原纤维降解与合成的失衡状态，从而达到稳定斑块的作用。

Molecular Mechanism of Effect of Wenban Humai Granule on Stability of Atheromatous Plaque

OBJECTIVE: To explore the molecular mechanism of wenban humai granule (WHG) in stabilizing atheromatous 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), alpha-smooth muscle actin (alpha-SMA) and collagen I (C-I) in model rabbits' neo-genesic intima were determined by immunohistochemical 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 alpha-SMA protein and C-I protein 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 alpha-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 synthesis thesis factors and down-regulating degradation factors, while simvastatin perform its action on plaque stability by down-regulating degradation factors alone.