血府逐瘀胶囊对动脉粥样硬化模型小鼠主动脉病变及CD47、PPAR-γ、NR1H3表达的影响  

Effects of Xuefu Zhuyu Capsules(血府逐瘀胶囊)on Aortic Lesion and Expression of CD47,PPAR-γand NR1H3 in Atherosclerosis Model Mice

作　　者：王曼曼 贾冬冬 张馨月 娄利霞[1] 吴爱明[1] 赵一舟[1] 国倩倩 杨睿 张冬梅[1] WANG Manman;JIA Dongdong;ZHANG Xinyue;LOU Lixia;WU Aiming;ZHAO Yizhou;GUO Qianqian;YANG Rui;ZHANG Dongmei(Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing,100700)

机构地区：[1]北京中医药大学东直门医院,北京市100700

出　　处：《中医杂志》2022年第17期1673-1678,1684,共7页Journal of Traditional Chinese Medicine

基　　金：北京中医药大学基本科研业务费项目(2019-JYBXS-167)。

摘　　要：目的探讨血府逐瘀胶囊治疗动脉粥样硬化(AS)的可能作用机制。方法30只载脂蛋白E基因敲除(ApoE^(-/-))小鼠随机分为模型组、血府逐瘀胶囊组、阿托伐他汀组,每组10只,另设10只C57BL/6N小鼠为正常组。除正常组外,其他各组小鼠均给予高脂饲料喂养6周制备AS早期模型。造模成功后血府逐瘀胶囊组给予血府逐瘀汤0.6 g/(kg·d)灌胃,阿托伐他汀组给予阿托伐他汀3.3 mg/(kg·d)灌胃,正常组和模型组给予0.3 ml去离子水灌胃,给药期间除正常组外其余各组继续给予高脂饲料喂养。干预12周后观察小鼠主动脉瓣病理形态学改变和脂质沉积情况;检测血脂指标[包括血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)],并计算TC/HDL-C、LDL-C/HDL-C和动脉粥样硬化指数(AI);检测小鼠主动脉整合素相关蛋白分子(CD47)、过氧化物酶体增殖物激活受体γ(PPAR-γ)、肝X受体α(NR1H3)蛋白表达水平。结果与正常组比较,模型组小鼠主动脉瓣斑块面积和脂质沉积增多,血清TC、LDL-C、TC/HDL-C、LDL-C/HDL-C和AI水平升高,主动脉CD47蛋白表达升高,HDL-C水平降低(P<0.01)。与模型组相比,血府逐瘀胶囊组和阿托伐他汀组主动脉瓣斑块面积和脂质沉积减少,小鼠血清TC、LDL-C水平及CD47蛋白表达下降,NR1H3蛋白表达升高(P<0.01),血府逐瘀胶囊组PPAR-γ蛋白表达水平升高(P<0.01);阿托伐他汀组HDL-C水平升高,TC/HDL-C、LDL-C/HDL-C和AI显著降低(P<0.05或P<0.01)。与阿托伐他汀组相比,血府逐瘀胶囊组CD47蛋白表达水平升高(P<0.05)。结论血府逐瘀胶囊治疗AS可能与调控炎症关键分子CD47、PPAR-γ、NR1H3的表达有关。Objective To investigate the possible mechanism of Xuefu Zhuyu Capsules(血府逐瘀胶囊)in the treatment of atherosclerosis(AS).Methods Thirty apolipoprotein E knockout(ApoE^(-/-))mice were randomly divid⁃ed into model group,Xuefu Zhuyu Capsules group and atorvastatin group,with 10 mice in each group,and 10 C57BL/6N mice were set as normal control group.Except for the normal group,mice were fed with high fat diet for six weeks to prepare early AS model.After successful modeling,the drug groups were given Xuefu Zhuyu Capsules 0.6 g·kg^(-1)·d^(-1)and atorvastatin 3.3 mg·kg^(-1)·d^(-1)by gavage,respectively.The normal and model groups were given 0.3 ml of de⁃ionized water by gavage.After 12 weeks of intervention,the pathological changes and lipid deposition of aortic valve in mice were observed.Blood lipid indexes including serum total cholesterol(TC),triglycerid(TG),low-density li⁃poprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C)were detected,and TC/HDL-C,LDL-C/HDL-C,and atherosclerosis index(AI)were calculated.The protein expression levels of aortic signal trans⁃ducer integrin-associated protein(CD47),peroxisome proliferator-activated receptorγ(PPAR-γ)and liver X receptorα(NR1H3)were detected by western blot.Results Compared to those in the normal group,the aortic valve plaque area and lipid deposition of mice in the model group increased,while serum TC,LDL-C,TC/HDL-C,LDL-C/HDL-C and AI levels,as well as aortic CD47 protein expression increased,and HDL-C level decreased(P<0.01).Com⁃pared to those in the model group,the aortic valve plaque area and lipid deposition in the Xuefu Zhuyu Capsules group and the atorvastatin group decreased,while the serum TC and LDL-C levels and CD47 protein expression decreased,and the NR1H3 protein expression increased(P<0.01).Moreover,the expression level of PPAR-γprotein in Xuefu Zhuyu Capsules group increased(P<0.01),while the level of HDL-C increased in atorvastatin group,and TC/HDL-C,LDL-C/HDL-C and AI were significantly reduced(P<0

关 键 词：动脉粥样硬化 血府逐瘀胶囊 炎症 血脂 

分 类 号：R285.5[医药卫生—中药学]