基于炎症免疫反应探究复方三七颗粒抗动脉粥样硬化作用机制

Preliminary Study on the Anti-atherosclerotic Inflammatory Immune Mechanism of Fufangsanqi-keli

目的:探究复方三七颗粒抗动脉粥样硬化作用机制。方法:将48只健康雄性ApoE-/-小鼠随机均分为空白对照组、模型组、立普妥组(1.5mg/kg.d)、复方三七颗粒低、中、高剂量组(7.5g/kg.d、14.5g/kg.d、21.5g/kg.d),造模成功后连续给药干预并观察28d。透射电镜下观察主动脉血管的结构变化;生化法及实时荧光技术(RT-qPCR)检测相关炎症指标的水平变化。结果:与空白对照组相比,模型组小鼠血管壁内脂质条纹沉积,平滑肌细胞增厚且排列紊乱,内皮细胞损伤、剥脱,可见数个巨噬细胞,其内泡沫细胞聚集;与模型组相比,各给药组平滑肌细胞及脂质沉积均有不同程度改善。与空白对照组相比,模型组小鼠IL-4、IL-10含量显著降低(P<0.01,P<0.05),TNF-α、IL-1β含量显著升高(P<0.01,P<0.05),TGF-β和LC3ⅡmRNA表达显著降低(P<0.01,P<0.05),ULK1 mRNA表达显著升高(P<0.01,P<0.05);与模型组相比,立普妥组及复方三七颗粒各剂量组IL-4、IL-10显著升高(P<0.01,P<0.05),TNF-α、IL-1β含量显著降低(P<0.01,P<0.05);TGF-β和LC3ⅡmRNA表达显著升高(P<0.01,P<0.05),ULK1 mRNA表达显著降低(P<0.01,P<0.05)。结论:复方三七颗粒对ApoE-/-小鼠动脉粥样硬化具有一定保护作用,其作用机制可能与上调IL-10、IL-4、TNF-α等抗炎因子水平,并上调主动脉TGF-β、LC3ⅡmRNA表达,同时下调IL-1β水平,从而保护主动脉血管免受炎症反应损伤有关。

Objective:To explore the anti-atherosclerosis mechanism of Compound Sanqi Granules.Methods:48 healthy male ApoE-/-mice were randomly divided into blank control group,model group,Lipitor group(1.5mg/kg.g/kg.d,14.5g/kg.d,21.5g/kg.d),continuous drug intervention and observation for 28 days after successful modeling.The structural changes of aortic vessels were observed under a transmission electron microscope;the level changes of related inflammatory indicators were detected by biochemical methods and real-time fluorescent technology(RT-qPCR).Results:Compared with the blank control group,the lipid stripes deposited in the blood vessel wall of the mice in the model group,the smooth muscle cells were thickened and arranged disorderly,the endothelial cells were damaged and peeled off,and several macrophages could be seen,and the foam cells in them aggregated;Compared with the control group,smooth muscle cells and lipid deposition in each administration group were improved to varying degrees.Compared with the blank control group,the contents of IL-4 and IL-10 in the model group were significantly decreased(P<0.01,P<0.05),and the contents of TNF-αand IL-1βwere significantly increased(P<0.01,P<0.05),the expression of TGF-βand LC3ⅡmRNA was significantly decreased(P<0.01,P<0.05),and the expression of ULK1 mRNA was significantly increased(P<0.01,P<0.05);compared with the model group,Lipitor group and compound In each dose group of Sanqi Granules,IL-4 and IL-10 were significantly increased(P<0.01,P<0.05),and the contents of TNF-αand IL-1βwere significantly decreased(P<0.01,P<0.05);TGF-βand LC3ⅡmRNA expression was significantly increased(P<0.01,P<0.05),and ULK1 mRNA expression was significantly decreased(P<0.01,P<0.05).Conclusion:Compound Sanqi Granules has a certain protective effect on atherosclerosis in ApoE-/-mice,and its mechanism may be related to up-regulating the levels of anti-inflammatory factors such as IL-10,IL-4,TNF-α,and up-regulating aortic TGF-β,LC3ⅡmRNA expression,while down-regulating the level of IL-1β,thereby protecting aortic vessels from inflammatory response injury.