The Effect Of Atorvastain On Atheromatous Plaque And Toll-like Receptor4Pathway In Atherosclerotic Rabbits

Objective:Our objective was to explore the effect of short-term different doses atorvastain on atheromatous plaque composion and stability, the expression of Toll-like receptor4(TLR4) protein and TLR4-dependent downstream signaling monocyte chemoattractant protein-1(MCP-1)、transforming growth factor-β(TGF-β) in an atherosclerotic rabbit model.Methods:Fourty male New Zealand White Rabbits were selected and randomized into the control group (n=10),model group (n=10),atorvastain low-dose group (n=10) and atorvastain high-dose group (n=10). Except for the control group,the others established atherosclerotic model by combining a8-week high fat diet feeding with aortaventralis balloon-dilation injury. After week8,the model group continued to give high fat diet,and the low or high dose atorvastain groups were given2weeks extra treatment with different doses drugs as lmg/(kg·d)or5mg/(kg·d) respectively. Blood samples were obtained at start of the study,before drug intervention and after drug intervention.At week10,all rabbits were sacrificed. Venous blood was drawn to measure serum lipid and using ELISA to quantify the amount of inflammation mediators MCP-1、TGF-β. HE,Masson and Sirius red stain were used to evaluate the amount of collagenous fiber and the pathophysiological changes of abdominal aorta. TLR4was observed by immunohistochemistry and western blot.Results::1.In control group vascular endothelial cells remain intact and arranged in neat rows. Internal elastic laminae intact. Medial membrane smooth muscle cells were clear,there were no obvious abnormalities.In model group, vascular endothelial cells fell off distinctly.Large number of macrophage-derived foam cells were accumulated under the intima. There was significant plaque with thin-cap fibroatheroma formation in the aortic. Comparaing with model group,the fibrous cap of vulnerable plaque thicken much in atrovastatin low-dose group. The degree of atheromatous in atrovastatin high-dose group was obviously decreased. A little part of endothelial cells fell off and foam cells under the intima were reduced. Medial membrane smooth muscle cells were arranged in order. Plaque had much more thicken-cap fibroatheroma than model group.2.At the end of the study,comparing with the other three groups,serum lipid and MCP-1of control group were significantly lower (P<0.05) and TGF-β were significantly higher (P<0.05). Serum lipid and MCP-1level were also obviously decreased in the two atorvastain groups than model group (P<0.05),and the reduce of atorvastain high-dose group was much more obviously (P<0.01). In the two atorvastain groups serum TGF-β were significantly increasing than model group (P <0.05),and the increasing of high-dose group was much more obviously (P<0.01).The expression of TLR4in control groups was lower than the other three groups (P<0.05).And they were obviously inhibited by high-dose atorvastain than low-dose atorvastain,comparing with the model group (P<0.01)Conclusion:1.Atorvastatin can regulate serum TG,TC,LDL-C level and stabilize vulnerable plaque by increasing collagen fiber content.2.Atorvastain could prevent the formation of atherosclerosis by inhibiting the expression of TLR4and regulating the release of its downstream signaling.3.Atorvastatin regulate serum TG,TC,LDL-C level and TLR4signaling pathway with a dose-dependent manner.