理气活血滴丸对ApoE^(-/-)小鼠动脉粥样硬化的干预作用及机制探讨  

Effect and mechanism of Liqi Huoxue Dripping Pill(理气活血滴丸)on atherosclerosis in ApoE^(-/-)mice

作　　者：郑玉华 许滔 雷雨 黄倩倩 龚韧 巫廷春 吕大沩 邓婷 穆春雨 ZHENG Yu-hua;XU Tao;LEI Yu;HUANG Qian-qian;GONG Ren;WU Ting-chun;LU Da-wei;DENG Ting;MU Chun-yu(Guizhou University of Traditional Chinese Medicine,Guiyang Guizhou 550003;Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine,Guiyang,Guizhou 550003,China;Guizhou Blood Center,Guiyang Guizhou 550002 China)

机构地区：[1]贵州中医药大学,贵州贵阳550003 [2]贵州中医药大学第二附属医院,贵州贵阳550003 [3]贵州省血液中心,贵州贵阳550002

出　　处：《时珍国医国药》2023年第7期1577-1581,共5页Lishizhen Medicine and Materia Medica Research

基　　金：国家自然科学基金(81960862);贵州省科技厅计划项目(黔科合平台人才[2017]5735号)。

摘　　要：目的研究理气活血滴丸对载脂蛋白基因E敲除(ApoE^(-/-))小鼠动脉粥样硬化的影响及相关机制。方法取SPF级雄性ApoE^(-/-)小鼠50只,予高脂饲料喂养造动脉粥样硬化模型,将造模成功的小鼠随机分为模型对照组、阿托伐他汀组及理气活血滴丸低、中、高剂量组。另C57BL/6J小鼠为正常对照组给予标准饲料喂养。第10周起,基于高脂饮食,理气活血滴丸低、中、高剂量组分别灌胃75、150、300 mg/(kg·d)理气活血滴丸,阿托伐他汀组灌胃2mg/(kg·d)阿托伐他汀,正常对照组和模型对照组给予普通饲料和予0.3ml的蒸馏水灌胃,持续给药4周后,取血清及主动脉。用全自动生化仪检测血清中甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)的含量;采用油红O染色观察主动脉弓根部病理变化,并分析计算管腔内斑块面积占比;应用Western Blot检测方法测定主动脉中YAP、p-YAP、TAZ及其下游蛋白JNK1/2、VCAM1的蛋白表达量。结果与正常对照组比较,模型组对照组小鼠主动脉内可见明显动脉粥样硬化斑块形成,模型对照组小鼠血清TG、TC、LDL-C、YAP、TAZ、JNK1/2、VCAM1表达水平显著升高,HDL-C、p-YAP表达水平显著下降(P<0.01或P<0.05),与模型对照组比较,理气活血滴丸各剂量组和阿托伐他汀组AS斑块面积占比、TG、TC、LDL-C、YAP、TAZ表达水平均显著下降,HDL-C、p-YAP表达水平均显著升高(P<0.01或P<0.05);理气活血滴丸中剂量组和阿托伐他汀组JNK1/2表达量不同程度减少(P<0.05),理气活血滴丸中、高剂量组和阿托伐他汀组VCAM1表达量不同程度减少(P<0.01)。结论理气活血滴丸具有降低AS模型小鼠血脂水平,减少主动脉AS斑块面积的作用,其机制可能与调控YAP/TAZ-JNK通路有关。Objective To investigate the effect of Liqi Huoxue Dripping Pills(LHDP)on atherosclerosis in E knockout(ApoE^(-/-))mice and its related mechanism.Methods A total of 50 SPF male ApoE^(-/-)mice were randomly divided into model control group,atorvastatin group and LHDP low-,medium-and high-dose groups.C57BL/6J mice were normal control group and were fed with standard diet.From week 10,based on high-fat diet,LHDP were administered orally with 75,150 and 300 mg/(kg·d)in LHDP low-,medium-and high-dose groups,respectively;atorvastatin group was given orally with 2mg/(kg·d)atorvastatin,normal control group and model control group were given ordinary diet and 0.3ml distilled water.After 4 weeks of continuous administration,serum and aorta were collected.The contents of triglyceride(TG),total cholesterol(TC),low density lipoprotein cholesterol(LDL-C)and high density lipoprotein cholesterol(HDL-C)in serum were detected by automatic biochemical analyzer.Oil red O staining was used to observe the pathological changes of aortic arch root,and the proportion of luminal plaque area was analyzed and calculated.The protein expressions of YAP,P-YAP,TAZ and their downstream proteins JNK1/2 and VCAM1 in aorta were detected by Western Blot.Results Compared with the normal control group,significant atherosclerotic plaque formation was observed in the aorta of mice in the model group,and the expression levels of TG,TC,LDL-C,YAP,TAZ,JNK1/2 and VCAM1 in serum of mice in the model group were significantly increased.The expression levels of HDL-C and P-YAP were significantly decreased(P<0.01 or P<0.05).Compared with the model control group,the proportion of AS plaque area,the expression levels of TG,TC,LDL-C,YAP and TAZ were significantly decreased in all three LHDP groups and atorvastatin group;the expression levels of HDL-C and P-YAP were significantly increased in all three LHDP groups and atorvastatin group(P<0.01 or P<0.05);the expression of JNK1/2 in LHDP medium dose group and atorvastatin group was decreased to different degrees(P<0

关 键 词：理气活血滴丸 动脉粥样硬化 斑块 通路 

分 类 号：R285.5[医药卫生—中药学]