短程大剂量阿托伐他汀对apoE^(-/-)小鼠动脉粥样硬化模型的作用

Effect of Short-Term High-Dose Atorvastatin on Atherosclerosis Model Established in apoE Knockout Mice

目的:探讨短程大剂量阿托伐他汀对于动脉粥样硬化(AS)斑块的干预机制。方法:选择4周龄雄性apoE^(-/-)小鼠高脂喂养6周建立AS模型,随机分为对照组、模型组、阿托伐他汀药物常规剂量组、中剂量组和高剂量组(负荷剂量组和非负荷剂量组)。2周后比较各组血脂水平、炎症因子浓度、血小板数目、血小板膜蛋白表达水平及斑块面积。结果:与模型组相比,对照组和阿托伐他汀药物各干预组HDL-C均显著增高,LDL-C均显著降低,血清及斑块内炎症因子水平明显下降,PLT均明显减少,CD31与CD62P荧光强度均显著降低(均P<0.05);负荷剂量组ox-LDL水平明显低于模型组(P<0.05)。阿托伐他汀药物各干预组斑块面积较模型组明显减小(均P<0.05)。结论:短程大剂量阿托伐他汀可能通过降低血脂水平,抑制相关炎症因子释放,调节血小板数目及血小板膜蛋白的表达来干预AS。

Objective:To explore the intervention mechanism of short-term high-dose atorvastatin on atherosclerotic(AS)plaque.Methods:Four-week-old male apoE^(-/-)mice were fed with high-fat diet for 6 weeks to induce AS.They were randomly divided into the control group,the model group,the atorvastatin conventional dose group,medium dose group and high dose group(loading dose group and non-loading dose group).The blood lipid levels,the concentration of inflammatory factors,the number of platelets,the expression level of platelet membrane protein and plaque area were analyzed at 2 weeks after treatment.Results:Compared with the model group,HDL-C was significantly increased,while LDL-C,serum and plaque inflammatory factors,PLT,CD31 and CD62 Pfluorescence intensity were all obviously decreased both in the control group and the atorvastatin intervention groups(all P <0.05).The level of ox-LDL in the loading dose of atorvastatin group was lower than that of model group(P<0.05).The plaque area in these atorvastatin intervention groups were significantly decreased than that of model group(all P <0.05).Conclusion:high-dose atorvastatin in short-term may interfere with AS by reducing blood lipid,inhibiting inflammatory factors,and regulating the number of platelets as well as the expression of platelet membrane proteins.