The Laboratory Study On HO/CO And NOS/NO Systems Of Diet-Induced Atherosclerosis In Rabbits And Drugs Interference

Objective: To study the changes of heme oxygenase/carbon monoxide and nitricoxide synthase/nitrogen monoxide systems of diet-induced atherosclerosis in rabbits. To administrate drugs to regulate the levels of serum lipids, serum nitrogen monoxide , plasma carbon monoxide and to regulate the expression of heme oxygenase-1 and inducible nitricoxide synthase in the thoracic aortic tissue of rabbit. To supply the experimental evidence for the prevention of atherosclerosis and guide clinical drug administration.Methods: 16 rabbits were divided into 4 groups (each group, n=4), control group, model group, amlodipine group and simvastatin group. The rabbits of the latter three groups were fed with 1% cholesterol diet and the control group was fed with normal diet for 8 weeks. Then all the rabbits were fed with normal diet for 8 weeks, and respectively administrated with amlodipine, simvastatin. The expression of heme oxygenase-1 and nitricoxide synthase in the thoracia aortic tissue were observed using immunohistochemistry technique. The levels of serum lipids , serum nitrogen monoxide and plasma carbon monoxide were obtained at the beginning, the 8th week, the 16th week. The expression of heme oxygenase-1 and nitricoxide synthase were measured quantitatively by MPI-500 Image Analysis System. The data were analysed with SPSS software: applied with ANOVA, the curative effect of drugs applied withpaired T-test. the linear correlation analysis of bivariate applied with Pearson. Results: The levels of serum lipids and plasma carbon monoxide of the model group were higher significantly than that of the control group (P<0.01),but the levels of serum nitrogen monoxide is reversal.Simvastatin lowered the levels of serum TC, TQ LDL,plasma CO and increased the level of serum HDL,NO significantly (P<0.01). There were no significant effects on the levels of serum lipids and nitrogen monoxide in amlodipine group (P>0.05). Increased levels of plasma carbon monoxide were reduced in rabbits administrated with amlodipine (P<0.01). The expression of heme oxygenase-1 and inducible nitrogen monoxide in the model group were much higher than that of the else (P<0.01). There were no significant different among the control group, the simvastatin group and the amlodipine group.The linear correlation analysis of between plasma CO and serum NO showed negative correlation (r=-0.753, <0.01).Conclusion:1 .The levels of serum lipids, plasma carbon monoxide and the expression of heme oxygenase-1 ,inducible nitricoxide synthase were significantly higher in the rabbits fed with cholesterol diet;but the levels of serum nitrogen monoxide were reversal.2.Simvastatin significantly reduced the levels of serum lipids,plasma carbon monoxide and the expression of heme oxygenase-1 and inducible nitricoxide synthase;but increased the levels of serum nitrogen monoxide.3.Amlodipine reduced the expression of heme oxygenase-1 and inducible nitricoxide synthase and the levels of plasma carbon monoxide; but it had not influence on the levels of serum lipids and nitrogen monoxide.