| Objectives: To establish a model of atherosclerosis rabbit fed with high fat diet. To investigate the expression of peroxisome proliferators-activated receptor gamma (PPARγ) in a rabbit model of atherosclerosis, and the effect of resveratrol. To explore the possible anti-atherogenic mechanism of resveratrol.Methods: seventy male New Zealand white rabbits were randomly divided into five groups: A,normal control group treated with normal sodium,B,pathological control group treated with normal sodium,C,pathological group treated with low dosage Res(4mg/ kg.d), D,pathological group treated with mid dosage Res(8mg/ kg.d), E,pathological group treated with high dosage Res(16mg/ kg.d). Rabbits in group A were fed with normal diet, Rabbits in groups B,C,D,E were fed with high fat diet. All rabbits were fed according to experiment design for 12 weeks. Serum TG, TC, LDC-C, HDL-C in rabbits were detected on the 0 and 12th week by biochemical method. The aortas were harvested for histopathological examination, and the intima-media thickness were measured. PPARγ,MCP-1,MMP-9 and TIMP-1 were examined by reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbentassay (ELISA).Results: (1) The blood lipid (TC, TG, LDL-C and HDL-C ) of pathological control group is higher than normal control group (P<0.01). Administration of Res could greatly decrease the levels of serum TC, TG and LDL-C (P<0.01) in dose-dependent way, but TC was not significantly decreased in group C(P>0.05). Res could greatly increased HDL-C in dose-dependent way in group C, D and E.(2) The atherosclerosis model with rabbits had been successfully established with 12 weeks'high fat diet. The endomembranes of aortic arch and thoracic aorta in pathological control group(B) are overlaid by large area AS plaques, however there are no plaques in normal control group; Administration of Res could diminish the area of plaque(P<0.05) in dose-dependent way.(3) In pathological control group(B), there are typical AS plaques in the superior segment of thoracic aorta and lots of infiltrating macrophages in AS plaques, Administration of Res could significantly lessen AS pathological changes(P<0.05) in dose-dependent way; there are no infiltrating macrophages in normal control group.(4) The mRNA expression of PPARγin AS plaques were progressively increased in group B when comparing to group A (P<0.01). The expression of PPARγin group C, D and group E were higher than in group B (dosage dependent).(5)Compared with group A, the mRNA and protein expression of MCP-1 and MMP-9 increased significantly in group B (P<0.01); they were significantly reduced in group C, D and group E (dose dependent) (P<0.01), but still higher than in group A (P<0.01).(6)The mRNA and protein expression of TIMP-1 significantly increased in group B when compared to group A (P<0.01). Administration of Res can increased the expression of TIMP-1 which were higher than in group B (P<0.05) (dose dependent).(7)The expression of PPARγmRNA in AS plaques was negatively correlated with the expression of MCP-1 and MMP-9﹙r=-0.727, r=-0.859; p<0.01).Conclusions: (1) Inflammatory reaction is important in the development of AS, including infiltration of inflammatory cells in vessel wall, synthesis of inflammatory mediators in circulation and AS plaques.(2) Res posseses anti-inflammatory effect on AS, because it could depress the serum TC, LDL-C and TG of AS Rabbits, heighten the level of HDL-C and TIMP-1, inhibit the infiltration of macrophages and the expression of MCP-1 and MMP-9 mRNA and protein.(3) Res could up-regulate the expression of PPARγmRNA in plaques after given AS rabbits for 12 weeks.
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