Effects of Atorvastatin Combined with CORM- 3 on Inflammation and Oxidative Stress Indexes in Atherosclerotic Vulnerable Plaque Model Rats / 中国药房

ABSTRACT

OBJECTIVE： To study the effects of atorvastatin combined with carbon monoxide releasing molecule 3 （CORM-3） on inflammation and oxidative stress indexes in atherosclerotic （AS） vulnerable plaque model rats. METHODS： The rats were randomly divided into control group （normal saline， i.g.）， model group （normal saline， i.g.）， statin group （atorvastatin 2 mg/kg，  i.g.）， and statin+CORM-3 group （atorvastatin 2 mg/kg， i.g.+CORM-3 10 mg/kg， i.p.）， with 8 rats in each group. Control group was fed with basal diet， and the right common carotid artery was exposed to surgery without injury and was treated with normal saline instead of drug； other three groups were fed with high-fat diet+right common carotid artery injury+heteroprotein injection to induce AS vulnerable plaque model， for 10 weeks； and then they were given relevant medicine for intervention， once a day， for consecutive 2 weeks. 24 h after last medication， abdominal artery blood was collected； the concentration of LDL-C and HDL-C were determined by fully automatic biochemical analyzer. The levels of hs-CRP， IL-10， MCP-1 and MMP-9 in plasma were detected by ELISA； plasma levels of MDA and oxidized low density lipoprotein （ox-LDL） were determined by chemical colorimetry； the protein expression of heme oxygenase-1 （HO-1） was determined by Western blot. The pathological changes of right common carotid artery were observed under light microscope. RESULTS： Compared with control group， the levels of LDL-C， hs-CRP， MCP-1， MMP-9， MDA and ox-LDL， and protein expression of HO-1 were increased significantly （P＜0.05）， while the levels of HDL-C and IL-10 were decreased significantly in model group （P＜0.05）； the right common carotid artery formed obvious AS plaques. Compared with model group， the levels of LDL-C， hs-CRP， MCP-1， MMP-9， MDA and ox-LDL were decreased significantly in statin group and statin+CORM-3 group in model group （P＜0.05）， while the levels of HDL-C， IL-10 and the protein expression of HO-1 were increased significantly （P＜0.05）. Except for LDL-C and HDL-C， the improvement of other indexes in statin+CORM-3 group was more significant than statin group （P＜0.05）； pathological changes of right common carotid artery in statin group were not obvious， but the pathological changes of rats in statin+CORM-3 group were significantly alleviated and plaque structure also tended to be more stable. CONCLUSIONS： Atorvastatin combined with CORM-3 is better than atorvastatin alone in improving inflammation and oxidative stress indexes of AS vulnerable plaque model rats， and can promote the stability of AS vulnerable plaques.