营心宁胶囊通过MEK1调控肝X受体促进动脉粥样硬化斑块稳定与消退的机制

Mechanism of Yingxinning Capsules Promoting the Stablilization and Regression of Atherosclerotic Plaque through Regulating Liver X Receptor Via MEK1

目的:探讨营心宁胶囊通过MEK1调控肝X受体促进动脉粥样硬化斑块稳定与消退的机制。方法:以雌性C57BL/6小鼠为研究对象,以营心宁胶囊作为丝氨酸-苏氨酸激酶MEK1/2抑制剂,将小鼠分为空白对照组,模型组,营心宁胶囊低、中、高剂量组。分别对小鼠肝脏、脾脏、肾脏、小肠和淋巴结,进行切片固定,对其血清进行生化分析;通过油红O染色对全动脉进行观察。以ApoE-/-小鼠构建胆固醇反向转运分析及动脉粥样硬化斑块分析。结果:与模型组比较,营心宁胶囊高剂量组血清中总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、谷丙转氨酶(glutamic pyruvic transaminase,ALT)和谷草转氨酶(glutamic oxaloacetic transaminase,AST)含量下降(P<0.05);随着营心宁胶囊浓度的增加,肝脏脂质积聚量明显减少;与空白对照组比较,模型组及营心宁胶囊低剂量组LXR mRNA表达量降低(P<0.05),营心宁胶囊中、高剂量组LXR mRNA表达量与空白对照组比较,差异无统计学意义(P>0.05)。用药组ApoE-/-小鼠的主动脉斑块面积及主动脉根部斑块面积比均下降且降低了TG在肝脏中的积累量。结论:营心宁胶囊对肝X受体动脉粥样硬化斑块稳定与消退具有促进作用。

Objective:To discuss the mechanism of Yingxinning capsules promoting the stabilization and regression of atherosclerotic plaque through regulating liver X receptor via MEK1.Methods:Female C57BL/6 mice were chosen as the objects of the research,Yingxinning capsules as serine threonine kinase MEK1/2 inhibitor,mice were divided into blank control group,the model group,low,moderate and high dosages groups of Yingxinning capsules.Liver,spleen,kidney,small intestine and lymph gland of the mice were sliced and fixed,the serum was analyzed by biochemistry;the whole arteries were observed by oil red 0 staining;ApoE-/-mice was used to perform reverse cholesterol transport analysis and atherosclerotic plaque analysis.Results:Compared with the model group,the contents of TC,TG,ALT and AST lowered in high dose group of Yingxinning capsule(P<0.05),as the concentrations of Yingxinning increased,the accumulation of lipid in liver decreased significantly;compared with blank control group,the expressions of LXR mRNA in the model group lowered(P<0.05),the difference had no statistical meaning when the expressions of LXR mRNA in moderate and high dosages groups were compared with these of blank control group(P>0.05).The ratio of the area of aortic plaque to the area of aortic root plaque decreased and it lowered the accumulation of TG in liver.Conclusion:Yingxinning capsules could promote the stabilization and regression of atherosclerotic plaque of liver X receptor.