The Study Of The Effects And Mechanisms Of Curcumin Together With Atorvastatin On Stabilizing Vulnerable Plaque

objective:To investigate the effects and mechanisms of curcumin together with atorvastatin on stabilizing vulnerable plaque.Methods : The 40 healthy male SD rats were fed for 1 weeks and then randomly divided into five experimental groups: control group(group A),model group(group B),atorvastatin group(group C),atorvastatin +curcumin group(group D),atorvastatin + curcumin + zinc protoporphyrin IX(ZnppIX)group(group E),each group with 8 mice,the experiment lasted for 12 weeks.The group A continued to fed with normal diets,then,to replicate the model of atherosclerosis vulnerable plaque,the other four groups rely on the method that fed with high-fat diets,and on the based drugs of propylthiouracil,vitamin D3 + liquid nitrogen freezing the right common carotid artery + injecting of xenogeneic globulin to promote immunological damage.After 10 weeks,the group A and B(the same amount of saline to intragastric administration + intraperitoneal injection),The group C(atorvastatin 2mg/kg to intragastric administration + same amount of saline intraperitoneal injection),the group D(atorvastatin 2mg/kg to intragastric administration +curcumin 100mg/kg to intragastric administration + same amount of saline intraperitoneal injection),the group E(atorvastatin 2mg/kg to intragastric administration +curcumin 100mg/kg to intragastric administration ++ZnPPIX 5mg/kg intraperitoneal injection)for 1weeks continuous interventions.Over the same period all rats were sacrificed immediately,The abdominal aortic blood was taken to test the expression of heme oxygenase-1(HO-1)protein,serum lipid index such as low density lipoprotein cholesterol(LDL-C),high density lipoprotein cholesterol(HDL-C),inflammation and oxidative stress index such as low oxidation densitylipoprotein(ox-LDL),matrix metalloproteinase-9(MMP-9),high sensitive C reactive protein(hs-CRP),monocyte chemoattractant protein-1(MCP-1),malondialdehyde(MDA),interleukin-6(IL-6)level changes,The middle segment of the right common carotid artery was intercepted with 10% neutral buffer formaldehyde solution and paraffin embedded.and the interception of right carotid artery segment in 10% implantation Fixed buffer formalin,embedded in paraffin,And the vessel cross section with hematoxylin and eosin(HE)staining,Observation of the size,morphology and structure of plaque under 200 times light microscope.Results: Compared with group A,the levels of LDL-C,ox-LDL,MMP-9,hs-CRP,MCP-1,MDA and IL-6 in B group were significantly higher than those in group A(P < 0.05),however,the level of anti atherosclerotic plasma lipoprotein(HDL-C)decreased(P < 0.05).The rats in the group A with carotid artery wall under light microscope intimal smooth,intact endothelium,elastic membrane fibers are arranged in a ring,the subendothelial,muscular layer and adventitia showed no lesions,intima,media and adventitia of three layer structure were normal,the rats in group B with carotid artery eye view visible light yellow plaque formation,Intimal thickening of the vessel wall was visible,visible local uplift,or with the injury,structural disorder,a large number of subendothelial lipid deposition,lipid core,reduce collagen content in plaque,thin fibrous cap,incomplete,visible foam cells and crystals are formed,and lymphocytes or macrophages infiltration,successful replication of AS vulnerable plaque model.Compared with the group B,blood lipid,inflammation and oxidative stress index in the group C such as LDL-C,ox-LDL,MMP-9,hs-CRP,MCP-1,MDA,IL-6 were decreased(P < 0.05),while the expression of HO-1 increased(P < 0.05),Compared with the group B,in the group C the wall showed localized eminence of the intima,thickening of the intima,but not the full wall of the wall.The number of intimal foam cells decreased,the fat nuclei became smaller,the smooth muscle fibers arranged slightly in the middle membrane,the fibrous caps were intact,the inflammatory infiltrating cells were reduced,and the plaque structure was improved.Compared with the group C,the LDL-C levels decreased,no significant changes in HDL-C levels in the group D(P > 0.05),but the expression of in HO-1 in the group D was higher than that of group C(P < 0.05),and the inflammation,oxidative stress index such as ox-LDL,MMP-9,hs-CRP and oxidation,MCP-1,MDA and IL-6 decreased(P < 0.05).The group D under light microscope vascular plaque group was more significantly improved compared with that of group C.The expression of HO-1 protein in group E and group D was equivalent,but the inflammation,oxidative stress index in group E such as ox-LDL,MMP-9,hs-CRP,MCP-1,MDA,IL-6 and B group was not significantly decreased but the expression similar or even higher,no significant improvement in vascular wall plaque under the light microscope,plaque area,intimal thickening,continuous endothelial damage results there were a lot of disorder,foam cells,inflammatory cell infiltration.Conclusion: 1)The comprehensive methods of combined use of high-fat fed + vascular frostbite + heterologous protein stimulated immune inflammatory can easily replicate rat vulnerable plaque model;2)Atorvastatin can inhibit AS and stabilize vulnerable plaques by regulating lipid and inducing HO-1 expression,but the effect of regular atorvastatin is relatively limited.3)Curcumin can efficiently induce the expression of HO-1 in together with regular atorvastatin,which could significantly enhance the ability of anti-inflammatory,anti-oxidant and stable vulnerable plaques.