The Study On The Anti-inflammatory Effect Of Pioglitazone On Atherosclerosis In Rabbits

ObjectiveThe aim of this study was to develop the model of atherosclerotic rabbit, to explore the anti-inflammatory mechanism of pioglitazone(PIO) on atherosclerosis(AS), and to afford evidences for the antiatherosclerotic therapy of PIO.MethodsNewzealand White Rabbits were divide into 5 groups: normal control, normal+ low dose of PIO, AS control, AS+low dose of PIO, AS+high dose of PIO. The models of AS rabbit were developed by high-lipid feeding plus impairing intima of abdominal aorta, then given placebo or PIO intervention. The blood lipid and the serum C reactive protein(CRP)were detected. immunohistochemistry was used to detected the infiltration of macrophage,the protein of intercellular adhesion molecule-1(ICAM-1)and peroxisome proliferator-activated receptorγ(PPARγ). Reverse transcription-polymerase chain reaction(RT-PCR) was used to detected the mRNA of ICAM-1 and PPARγ. The analysis of variance(ANOVA) or non-parametric test of the SSPS software package were used to analyses the data.The value of p<0.05 was statistically considered significant .Results1.The blood lipid(TC, TG, LDL-C and HDL-C )of AS control is higher than normal control(P<0.05). High and low dose of PIO could depress the TG of AS rabbits(P<0.05), the decreasing amplitude in high dose of PIO group is more than low dose. High and low dose of PIO could heighten the HDL-C of AS Rabbits(P<0.05), the heightening amplitude in high dose of PIO group is more than low dose(P<0.05).2. The serum CRP of AS control is higher than normal control(P<0.05); high and low dose of PIO could depress the CRP of AS Rabbits(P<0.05), the decreasing amplitude in high dose of PIO group is more than low dose group(P<0.05).3.The endomembranes of aortic arch and thoracic aorta in AS control group are overlaid by large area AS plaques, however there are not plaques in normal control group; high and low dose of PIO could diminish the area of plaque(P<0.05), the diminishing amplitude in high dose of PIO group is more than low dose group(P<0.05).4. There are typical pathological changes in the middle pieces of abdominal aorta in AS control group, high and low dose of PIO could lessen AS pathological changes.5.There are lots of infiltrating macrophages in AS plaques in AS control group, but no macrophage in vessel walls in normal control group(P<0.05). High and low dose of PIO could inhibit the infiltration of macrophages in plaques(P<0.05), the inhibiting amplitude in high dose of PIO group is more than low dose group(P<0.05).6.There are large quantity of expressing ICAM-1 protein and mRNA in AS plaques in AS control group, but small quantity of them in normal control group(P<0.05). High and low dose of PIO could inhibit the expression of ICAM-1 protein and mRNA (P<0.05), the inhibiting amplitude in high dose of PIO group is more than low dose group(P<0.05).7. There are large quantity of expressing PPARγprotein and mRNA in AS plaques in AS control group, but small quantity of them in normal control group(P<0.05). High and low dose of PIO could inhibit the expression of PPARγprotein and mRNA (P<0.05), the inhibiting amplitude in high dose of PIO group is more than low dose group(P<0.05).Conclusions1. Inflammatory reaction is important content of AS, including infiltration of inflammatory cells in vessel wall, synthesis of Inflammatory mediators in circulation and AS plaques.2. PIO posseses anti-inflammatory effect on AS, because it could depress the serum CRP and TG of AS Rabbits, heighten the HDL-C, inhibit the infiltration of macrophages and the expression of ICAM-1 mRNA and protein.3. PIO could down regulate the expression of PPARγmRNA and protein in plaques after given AS rabbits for 8 weeks.