Effects Of Rosiglitazone On Interleukin-6and Interleukin-8Expression In Rabbits With Early Arteriosclerosis

Background and Objective Studies have shown that peroxisome proliferator-activated receptor gamma (PPAR-y) play an important role in the control of metabolism, inflammation and thrombosis. Recent study found that PPAR-y agonists such as thiazolidnediones (TZDs) play the role of protecting the cardiovascular and slow atherosclerosis duration through its anti-inflammatory and anti-oxidative stress effects, but its mechanism is not very clear. This study aim to comparison the effect of rosiglitazone and simvastatin on the expression of interleukin (IL)-6and interleukin(IL)-8in atherosclerotic rabbits model and to explore the anti-atherosclerotic properties of rosiglitazone,provide a theoretical basis for clinical prewention and treatment of atherosclerosis.Methods36healthy pure New Zealand white rabbits, male, body weight2.0±0.15kg, were randomly divided into control group, model group, simvastatin group and rosiglitazone group, af ter one week of the adaptive feeding. Control group, only to be fed with normal diet, the other three groups fed with high fat diet containing2%cholesterol and5%lard, at the same time subcutaneous injection of homocysteine thiolactone (HTL)20mg·kg-1d-1, after four weeks stop the HTL and continue feeding the high fat diet two weeks to establish the AS model. After the end of the modeling, the simvastatin group given simvastatin3mg·kg-1d-1; rosiglitazone group given rosiglitazone0.5mg·kg-1d-1; model group and the control group were given normal saline for4weeks. After ten weeks of the experiment, the serum IL-6and IL-8levels of the marginal ear vein blood was detected through enzyme linked immuno-sorbent assay(ELISA), enzymatic detection of serum lipid levels; take the specimen of the aortic arch, the sections were hematoxylin eosin (HE) staining and use immunohistochemical methods detect rabbit aortic atherosclerotic tissue IL-6and IL-8expression levels. Results Compared with the control group, each group lipids was significantly increased (P<0.01); Compared with model group, simvastatin group TC,TG and LDL-C was significantly lower (P<0.01), HDL-C significantly increased (P<0.01), rosiglitazone group LDL-C was significantly lower(P<0.01), HDL-C significantly increased (P<0.01), TC and TG, are no significant difference (P>0.01); compared with the simvastatin group,TC, LDL-C of rosiglitazone group was significantly increased (P<0.01), TG and HDL-C are no significant difference (P>0.01). Compared with control group, the serum IL-6, IL-8levels were significantly increased (P<0.01) in the other three groups; Compared with model group, the rosiglitazone group serum IL-6, IL-8levels were significantly decreased (P<0.01), the simvastatin group, IL-6, IL-8levels also decreased (P<0.01); the rosiglitazone serum IL-6, IL-8levels lower than the simvastatin group, there was significant difference (P<0.01). HE staining of biopsy shown that:the control group animals aortic intima, tunica media, and the outer membrane structure is clear;the model group seen a large number of foam cells under the aortic intima, while a small amount of fibrous tissue proliferation, formation of a huge patch of the convex, containing a large number of foam cells, inflammatory cells; the simvastatin group aortic lesions are lighter, and only see a small amount of foam cells under the intima, form a low continuity fatty streak lesions; rosiglitazone lesions are similar with the simvastatin group, but more lighter. The aortic specimens were detected by immunohistochemistry showed that:compared with the control group, the IL-6,IL-8levels of the other three groups were significantly increased (P<0.01); Compared with model group, simvastatin and rosiglitazone group IL-6, IL-8expression level was significantly lower (P<0.01); rosiglitazone group IL-6, IL-8expression levels compared with the simvastatin group were lower (P<0.01).Conclusion Both rosiglitazone and simvastatin can resistance to atherosclerosis, simvastatin can adjustment dyslipidemia while rosiglitazone could reduce the expression of the inflammatory factor such as IL-6and IL-8both in the serum and the diseased region then alleviated the inflammatory reaction.