| [Background] Atherosclerosis is an inflammatory disease and inflammation mediates its all stages, from initiation to progression. Many of the cardiovascular events were caused by plaque rupture and thrombosis. So one of the most important measures for us to prevent and cure cardiovascular and cerebrovascular diseases was to restrain inflammatory reaction and stabilize plaque.Inflammation contributes to the formation and progression of atherosclerosis. Mononuclear cells, macrophages and lymphocytes were all involved in inflammatory process, and they generated many cytokines, adhesion molecules, mediators of inflammation and so on, such as interleukin-1β, interleukin-6, tumor necrosis factor-αand interferon-γ. Furthermore,interferon-γcan induce macrophages and smooth muscle cells to express matrix metalloproteinase especially matrix metalloproteinase-2 and -9, which were the main cytokines degrading collagen of fibrous cap and destroying the stability of plaque.Nuclear factor-kappa B is one of the key factors to regulate genetic transcription and it can activate macrophages, T lymphocytes and smooth muscle cells, and then result in releasing of kinds of biomolecules, cytokines, and growth factors and so on.Tea polyphenols, extracted from tea, is the main active components of pharmacodynamic actions. Multiple researches indicate that tea polyphenols play an important role in anti-oxygen, anti-lipid peroxidation, clearing free radicles, anti-mutation and anti-tumor formation, relatively little knowledge is available related to its anti-inflammatory action and so mechanisms of this action is unclear.[Objective] In this study, we induced the rabbit AS model to observe effects of tea polyphenol on the expression of inflammatory factors TNF-α, IL-1β, NF-κB, and MMP-2, 9 in atherosclerotic plaques, and then to ascertain mechanisms of its antiatherosclerotic action, therefore, to provide the therapeutic and experimental basis to clinical coronary artery disease and complications.[Methods] Thirty male New Zealand rabbits were randomly allocated into five groups, with six in each group: 1, normal control group (NC group); 2, AS group; 3, TP group; 4, Asp group; 5, Sim group. The rabbits in NC group were fed with basic forage. The rest four groups were fed with high-fat forage. Additionally, every day, rabbits in TP group were fed with tea polyphenols 1.2g/kg; rabbits in Asp group were fed with Aspirin 12.5mg/kg; rabbits in Sim group were fed with Simvastatin 5mg/kg; Every animal have its own cage, and have enough water to drink in. Each animal was fed with forage about 60g one day. Their weights were measured once a week so as to adjust their food-intake promptly. They were fed for 12 weeks in all. Blood samples were collected from the marginal vein of the ear before experiment and at the end of 12 week respectively and serum TC, TG, LDL-C and HDL-C level were examined and then AI were calculated. The histomorphology of the aorta was observed by HE stain and MASSON stain. The IT, MT, I/M and atherosclerotic area ratio were measured by image analysis software. The protein expression of NF-κB, TNF-α, IL-1β, MMP-2 and MMP-9 were detected by immunohistochemitry staining. The mRNA levels of TNF-αand MMP-2 were detected by reverse transcription-polymerase chain reaction (RT-PCR).Data were expressed as mean±S.D. A value of P<0.05 was considered statistically significant.[Results]①There were no significant difference in the level of weight and serum TC, TG, LDL-C and HDL-C among each group at the beginning of experiment. At the end of twelfth week, the levels of weight, TC, TG, LDL-C, HDL-C and AI in each group were higher than those in the beginning(P<0.05);Furthermore, the levels of serum TC, TG, LDL-C and AI in the four high- cholesterol diet groups were significantly higher than those in normal control group(P<0.05); Compared with AS group, the levels of serum TC, TG, LDLC and AI in TP group were decreased(P<0.05), but the level of serum HDL-C was increased(P<0.05).②Compared with NC group, the degree of aortic intima damage, lipidoses and inflammatory cell infiltration were all increased in the rest four groups (P<0.05). Compared with AS group, the degree of aortic intima damage, lipidoses and inflammatory cell infiltration were decreased in TP group (P<0.05). There were no difference among TP group, Asp group and Sim group.③Compared with NC group, the levels of intima thickness and medium thickness were increased differently in the rest four groups, as well as atherosclerotic area ratio. The levels of those were the highest in AS group. Compared with AS group, the levels of those were significantly lessened in TP group (P<0.05). There were no difference among TP group, Asp group and Sim group.④Compared with NC group, the levels of NF-κB, TNF-α, IL-1β, MMP-2 and MMP-9 protein were increased in model group(P<0.05). Those were diversely lessened in TP group, Asp group and Sim group compared with AS group (P<0.05).⑤Compared with NC group, the levels of TNF-αand MMP-2 mRNA were obviously increased in model group(P<0.05). Those were diversely lessened in TP group, Asp group and Sim group compared with AS group (P<0.05).[Conclusions] 1. Atherosclerosis is a chronic inflammatory process.2. Tea polyphenols can inhibit the progression of atherosclerotic lesion obviously.3. Tea polyphenols may take effects on anti-atherosclerosis through inhibiting inflammatory reaction and stabilizing plaque.
|
PDF Full Text Request