| Objective:To investigate the possible mechanisms of Bushen huoxue Recipe in preventing and treating Atherosclerosis and atherosclerosis plaque through observing plasma lipid levels, changes of the aortic wall tissue morphology and ultrasturcture, detects the variation of inflammatory factor MMP-1,-2,-3,-8,-9,12, CD40protein expression, and the influence of NF-κ B activation and the apoptosis of vascular smooth muscle cells.Methods:AS model was induced by a special feeding high-fat diet using two kind of experimental animal quail, New Zealand rabbits after forming hyperlipidemic.(1) Through the different time detection of lipids include Cholesterol (CHOL), Triglycerides (TG), low-density lipoprotein (LDL) and high-density lipoprotein (HDL), to dynamically observate the effection of Bushen huoxue Recipe on the lipid level in experimental model;(2) observationof sections of aortic wall stained with HE;(3) observate of the immunohistochemistry of the protein level of inflammatory factor MMPs, CD40and the effection of the actival NF-κB. Results:(1) Establish the AS animal model animals quail and rabbits are successfully copied the AS model. The animal model shows significant AS plaques, spotty or sheet of milky white uplift, located in the aortic sinus to aortic arch segment, thoracic and abdominal aortic lessions also obvious in AS rabbit model. The normal group does not see AS lesion, and intimal wall seems smooth and stretchable.(2) The influence of experimental animal lipids for Bushenhuoxue recipe In quail experiment, after12weeks, Bushenhuoxue Recipe high-dose group of cholesterol (CHOL), TG, LDL-C level is lower compared with model group (P<0.05), and TG is more obvious; HDL-C/LDL-C is higher than model group (P<0.05), AI is lower than model group (P<0.05); lipid-lowering effect is not obvious in middle-dose group and low-dose group, prompting that Bushenhuoxue Recipe has a certain effect on lowering lipid and has a dose dependent manner. In rabbit experiments, each lipid in Bushenhuoxue Recipe is lower than the model group. When administered eight weeks, compared with model group, rabbit serum cholerterol, TG and LDL-C is significantly lower (P<0.05); serum HDL-C, HDL-C/LDL-C, AI values have no significant different.(3) The pathology morphous of AS plaque normal aortic intima is smooth, complete and no cell infiltration. The intimal in model group sooms thicken, has plentiful foam cells, smooth muscle cell is derangement, the fracture of the internal elastic laminae; both Bushenhuoxue Recipe and positive group AS lesions is lighter and smaller of plaque formation range.(4) The effect of MMPs, CD40, NF-κB protein expression in AS plaque Bushenhuoxue Recipe can inhibite or down regulate the expression of MMP-1, MMP-2, MMP-3, MMP-9, MMP-12, especially for MMP-2, MMP-3(P<0.05); Bushenhuoxue Recipe be significantly inhibite the expression of CD40(P<0.01); and aslo inhibite NF-κB protein, but has no significant differences.(5) Compared among MMPs, CD40, NF-κB protein expression in model group, the correlation coefficients of MMP-1and MMP-2, MMP-8 and MMP-9, MMP-12, mmp-2and CD40, NF-κB and CD40are0.935,0.809,0.942,0.833,0.866, and aslo have a significant level (P<0.05). Besides the correlation coeffcients of MMP-1and CD40, MMP-3and MMP-8, MMP-9, MMP-12are0.675,0.737,0.628,0.731, showing a weak correlation, but there is no significant difference.Conclusion:(1) Bushenhuoxue Recipe has a certain lipid-lowering effect with dose-dependent manner, showing to cut down serum TG, CHOL, LDL-C, to heighten HDL-C slightly. Sugesting Bushenhuoxue Recipe has a weak anti-artherosclerosis role.(2) Bushenhuoxue Recipe can inhibite or downward the MMPs protein expression, especially for MMP-2, MMP-3.(3) Bushenhuoxue Recipe can reduce the inflammation factor of CD40, NF-κB, and has a certain anti-inflammatory effects.(4) There is a certain correlation among MMPs, CD40, NF-κB, showing Bushenhuoxue Recipe may inhibite NF-κB activation and block CD40-CD40L system. |
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