| BackgroundThe cardiovascular and cerebrovascular diseases have a important pathology basis to cause the disease brusting, that is owing to the atherosclerotic plaque rupturing and causing ulcers, then secondary thrombosis in lumens.How to improve big lipoid core and thin fibrous cap of the instability plaque and stablize them? It will be the main goal preventing the arteriosclerosis. It was showed in recent study that inflammatory reaction was the basis factor causing instability plaque. The statins had some effect. In our study, based on the the theory of pathogenesis of the phlegm and the stasis in Chinese Medicine and the inflammatory pathology basis of the arteriosclerosis, we suggested the idea of toxin for treatment and using Si Miao Yong An Decoction which has the function of blood quickening and toxin resolving to intervention the arteriosclerosis.ObjectiveTo study the effect and correlated mechanism of Si Miao Yong An Decoction on plaque stability of ApoE gene-knockout (ApoE-/-) mice. According to observing the result of Si Miao Yong An Decoction on plaque stability of ApoE-/- mice, we will investigate the mechanism of action and search the theory evidence for treating the arteriosclerosis in clinic.MethodWe made the arteriosclerosis models by high-fat diet.At first, Fourty-five ApoE-/- mice which were7-8 week age were fed a high-fat diet for 13 weeks.Thereafter, we choiced randomly four mice to observe their basis arteriosclerosis pathology.The rest were randomized to four groups (10 in each group):model group, Simvastatin group, low decoction group(low dose of Si Miao Yong An Decoction group), large decoction group(large dose of Si Miao Yong An Decoction group).Except the Model group fed by normal sodium, the other group fed by corresponding medicine. Another 10 mice (C57BL/6J) was served as a normal control group.Then, all the mice were sacrificed after thirty- two week, their blood was collected by removaling the eyeballs.Following that, take out of the heart and arteriae aorta to fixed them. According to the Suzuki methods, we collected four slices in same surfacing of aortic root. Next, Movat stain, HE stain and Sirius red picro-polarization method and immunohisto chemistry stain respectively in contiguous slices.Then, we observed the following:1.The morphology and composition of atherosclerotic plaques in aortic roots were investigated, and emphasised the size of lipoid core and thin fibrous cap (including the thickness, succession the collogen content of the plaques). And evaluating the positive areas expressed by smooth muscle cells and macrophage in plaque with immunohisto chemistry stain.The plaque area, lipide out of the cells and in the plaque, collagen content and percent area of plaque were all evaluated by the software of IPP image analisis. The semiquantitative analysis were taken for pathology of morphologic change.2. Detectting blood-fat level by automatic biochemistry machine.3.Detectting inflammation interleukin.-1β(IL-1β) by enzyme sandwich method, CD68,IL-1β,nuclear factor-κB(NF-κB), activation receptorγ(PPAR-γ) of peroxisome vegetation (PPAR-γ), transforming growth factor-β1(TGF-β1) and vascular endothelial growth factor (VEGF) immunohistochemistry stain.Resultl.ApoE-/- mice which were fed a high-fat diet for 32 weeks formed instability plaque in aortic root.The plaques were with big lipoid core and thin fibrous cap and less collogen contents.2.Comparing to model groups, large decoction group(large dose of Si Miao Yong An Decoction group) increased the plaque thickness, the pathology morphous was mainly fibrous plaque. TGF-β1 indicated increasing trend in plaque, but VEGF indicated dropping trend in plaque.3.Comparing to model groups, large decoction group(large dose of Si Miao Yong An Decoction group) increased blood fat. TC are higher than that of model group.4.Comparing to model groups, large decoction group(large dose of Si Miao Yong An Decoction group) increased significantly the expression of NF-KBp65 proteinum in plaque (P<0.05).CD68 and IL-1βall indicated raising trend (P>0.05).On the opposite, low decoction group(low dose of Si Miao Yong An Decoction group) decreased significantly the expression of IL-1β(P<0.05), CD68 and NF-κBp65 in plaque indicated dropping trend (P>0.05).5.Comparing to model groups, in low decoction group(low dose of Si Miao Yong An Decoction group), the plaque showed small area of lipoid core and increased significantly collogen content (P<0.05).The effect was better than control group.ConclusionApoE-/- mice which were fed a high-fat diet for 32 weeks formed plaque in aortic root with the characteristic of instability plaque.Si Miao Yong An Decoction with the function of blood quickening and toxin resolving has the effect of stabilized plaques, but the different effect is according to different dose. Low dose of Si Miao Yong An Decoction can control lipin core area and increase collogen content. Large dose of Si Miao Yong An Decoction can form fibrous plaque.Thereofore, low dose of Si Miao Yong An Decoction has better effect to control inflammation than that of large dose of Si Miao Yong An Decoction.
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