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目的探讨短期内不同剂量阿托伐他汀对动脉粥样硬化家兔模型toll样受体4(TLR4)的表达及其下游信号单核细胞趋化蛋白(MCP-1)、转化生长因子β(TGF-β)血清水平的影响。方法 28只新西兰大白兔随机分为对照组(n=6)、模型组(n=6)、阿托伐他汀低剂量组(n=8)和阿托伐他汀高剂量组(n=8)。除对照组外其他各组均通过8周高脂喂养联合腹主动脉球囊损伤术建立动脉粥样硬化模型。8周后,模型组继续高脂喂养,阿托伐他汀低、高剂量两组在高脂喂养的同时分别给予不同剂量药物干预2周。10周处死所有动物。静脉血测定血清血脂水平及ELISA法测定炎性因子MCP-1、TGF-β的血清水平。HE、Masson染色和天狼猩红染色观察血管病理变化及胶原纤维含量,免疫组化检测TLR4的表达水平。结果对照组血脂水平和炎性因子MCP-1水平明显低于其他各组(P<0.05),TGF-β水平明显高于其他各组(P<0.05)。阿托伐他汀低、高剂量两组血脂及MCP-1水平明显低于模型组(P<0.05),TGF-β水平明显高于模型组(P<0.05),且高剂量组变化更加明显(P<0.01)。对照组TLR4的表达明显低于其他各组(P<0.05),阿托伐他汀低、高剂量组显著低于模型组(P<0.05),且高剂量他汀组比低剂量组降低更为显著(P<0.01)。结论阿托伐他汀可在短期内降低血脂,同时通过减少TLR4的表达及调节下游信号MCP-1、TGF-β的释放发挥抗动脉粥样硬化作用,且具有剂量依赖性。
Objective To investigate the effects of different doses of atorvastatin on toll-like receptor 4 (TLR4) and its downstream signal monocyte chemoattractant protein (MCP-1), transforming growth factor β (TGF) -β) serum levels. Methods Twenty-eight New Zealand white rabbits were randomly divided into control group (n = 6), model group (n = 6), atorvastatin low dose group (n = 8) and atorvastatin high dose group . In addition to the control group, all other groups were given atherosclerosis model by 8-week high-fat diet and abdominal aorta balloon injury. After 8 weeks, the model group continued to be fed with high fat. Atorvastatin low and high dose groups were administered with different doses of medications for 2 weeks while being fed with high fat diet respectively. All animals were executed at 10 weeks. Serum lipid levels were measured by venous blood and serum levels of MCP-1 and TGF-β by ELISA. HE, Masson staining and Sirius red staining were used to observe the vascular pathological changes and collagen fibers. The expression of TLR4 was detected by immunohistochemistry. Results The levels of serum lipids and MCP-1 in the control group were significantly lower than those in other groups (P <0.05). The levels of TGF-β in the control group were significantly higher than those in other groups (P <0.05). The levels of serum lipids and MCP-1 in atorvastatin low and high dose groups were significantly lower than those in model group (P <0.05), and the levels of TGF-β in model group were significantly higher than those in model group (P <0.05) P <0.01). The expression of TLR4 in the control group was significantly lower than that in the other groups (P <0.05). Atorvastatin low and high dose groups were significantly lower than the model group (P <0.05), and the high dose statin group decreased more significantly than the low dose group (P <0.01). Conclusions Atorvastatin can reduce blood lipids in a short period of time and exert anti-atherosclerotic effects by decreasing the expression of TLR4 and regulating the release of downstream signals MCP-1 and TGF-β in a dose-dependent manner.