The Mechanism Study Of Garlicin On Anti-unstable Atherosclerotic Plaque In ApoE^-/- Mice

Objective: To investigate the influence of garlicin on the stability of atherosclerotic plaque in apolipoprotein E gene knockout(apoE^-/-)mice induced by high fat diet and to explore the possible mechanisms from the perspective of anti-inflammation and anti-apoptosis of gailicin in inhibiting the progress of atherosclerosis.Methods: 24 healthy apoE^-/-male mice aged 8 weeks were chosen in our experiment,weight 20-22 g,after 1 week adaptive feeding,they were fed with high cholesterol diet for8 weeks to establish atherosclerotic models,then were randomly divided into low-dose galicin group,high-dose galicin group and model-group,8 mice in each group,mice in high-does group were given 0.5ml galicin by gavage,the low-does group received 0.25 ml galicin and 0.25 ml normal saline?0.9%?by ig.Model group were given the same volume of normal saline?0.9%?respectively.All the mice were sacrificed after 8 weeks of intervention of galicin.Eye-ball blood were collected to measure the Total cholesterol?Triglyceride?Low density lipoprotein cholesterol?High density lipoprotein cholesterol and C-reactive protein in serum by enzyme linked immunosorbent assay methods,the aortic root were separeted or pathological statining.The pathological changes in atherosclerotic plaque were observed by haematoxylin-eosin staining,the cell apoptosis were detected by Td T-mediated d UTP nick end labeling methods,the contents of collagen were detered by Sirius red staining,and the expression level of macrophage,vascular smooth muscle cells?vascular smooth musclcells?,apoptosis-ass-oicated protein cell lymphoma/leukmia-2?Bcl-2?,B cell lymphoma/leukmia-2 associated X protein?Bax?and cysteinyl aspartate specificproteinase-3?Caspase-3?were evaluated by immunohistochemistry staining.Applying all the data for Normality test and Homogeneity test of variances.The data which meet the conditions using Chi-square test to contrast.While the data which do not meet the conditions using the Rank-sum test instead.All the results are showed by ?x|-?±s.P<0.05 means the difference is statistically significant.Results: There were no significant differences in blood lipid and weight among three groups before and after experiment?P>0.05?;Compared with model group,the inflammatory cell C-reactive protein was lower in garlicin group?P<0.01,P<0.05?;Haematoxylin-eosin staining showed large amount of foam cells and Cholesterol crystal in model group,while the area of atherosclerotic plaque decreased and the structure of plaque became more stable in low-does garlicin group?P<0.01?;Td T-mediated d UTP nick end labeling statining revealed low-does garlicin treatment could suppress the area of apoptosis definitely?P<0.05?,although high does garlicin group showed the tendency of reduction,the difference had no statistical significance?P>0.05?;Sirius red staining analysis found garlicin could increase the content of collagen significantly?P<0.05?;Moreover,immunohistochemistry staining observed that low-does garlicin attenuated the accumulation of macrophage,inhibited the expression of Bax?Caspase-3,accompanying with an activation in Bcl-2 protein level?P<0.01?,and there were statistical difference between low does and high does garlicin?P<0.05?,however,garlicin had no effect on the content of vascular smooth muscle cells?P>0.05?.Conclusions: Allicin can effetely stabilize and control the progress of the atherosclerotic plaque in apoE^-/-mice,the mechanism maybe related with the inhibition of inflammation and the regulation of apoptosis.