四妙勇安汤通过拮抗Ox-LDL脂代谢途径对ApoE^(−/−)小鼠动脉粥样硬化颈动脉斑块的影响  

Effect of Simiao Yongan Decoction on atherosclerotic carotid plaque in ApoE^(−/−) mice via antagonizing Ox-LDL lipid metabolism pathway

作　　者：高照 许心蕊 金秋硕[1] 孙浩[2] 孙克寒 杨漫芳 张晴玥 李洋[3] 娄利霞[1] 吴爱明[1] 聂波[1,3] GAO Zhao;XU Xin-rui;JIN Qiu-shuo;SUN Hao;SUN Ke-han;YANG Man-fang;ZHANG Qing-yue;LI Yang;LOU Li-xia;WU Ai-ming;NIE Bo(Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing,Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine,Beijing 100700,China;Department of Pathology,Dongzhimen Hospital of Beijing University of Chinese Medicine,Beijing 100700,China;School of Traditional Chinese Medicine,Beijing University of Chinese Medicine,Beijing 100029,China)

机构地区：[1]北京中医药大学东直门医院中医内科学教育部和北京市重点实验室,北京100700 [2]北京中医药大学东直门医院病理科,北京100700 [3]北京中医药大学中药学院,北京100029

出　　处：《海南医学院学报》2022年第14期1050-1058,共9页Journal of Hainan Medical University

基　　金：国家自然科学基金面上项目(81874446);国家科技重大专项课题(2017ZX09304019)。

摘　　要：目的:探讨四妙勇安汤通过拮抗氧化低密度脂蛋白(Ox-LDL)脂代谢途径对ApoE^(−/−)小鼠动脉粥样硬化颈动脉斑块的干预作用及机制。方法:采用2周高脂喂养+右侧颈总动脉外置套管术+8周高脂饲养制备ApoE^(−/−)小鼠动脉粥样硬化颈动脉斑块模型。实验共分为5组,假手术组和模型组去离子水灌胃,其余各组分别为四妙勇安汤组、吡格列酮组和阿托伐他汀组。全自动生化仪对血清中总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)及低密度脂蛋白胆固醇(LDL-C)水平检测;酶联免疫法对血清OxLDL含量测量;颈动脉应用苏木素-伊红染色察看其病理形态学变化,并对颈动脉参数测定;采用免疫组化和免疫印迹法分别检测小鼠颈动脉组织中脂肪酸结合蛋白4(FABP4)含量以及过氧化物酶体增殖物激活受体γ(PPARγ)、基质金属蛋白酶-2(MMP-2)的蛋白变化。结果:与假手术组对比,模型组小鼠血清HDLC升高(P<0.05);与模型组比较,四妙勇安汤组和阿托伐他汀组TC、LDL-C均升高(P<0.05),HDL-C均降低(P<0.05);吡格列酮组HDL-C降低(P<0.05),LDL-C升高(P<0.05)。相比假手术组,模型组小鼠血清Ox-LDL含量增加,颈动脉的内膜厚度(IT)、内膜比中膜厚度(IT/MT)、斑块面积(PA)、斑块面积比血管管腔面积(PA/LA)均增加(P<0.05);免疫组化和WB结果显示FABP4和MMP-2蛋白表达增加,PPARγ蛋白表达减少。与模型组比,四妙勇安汤组、吡格列酮组和阿托伐他汀组血清Ox-LDL含量减少(P<0.05),颈动脉IT、IT/MT和PA/LA减少(P<0.05);免疫组化和WB结果显示各给药组FABP4和MMP-2蛋白表达均减少,PPARγ蛋白表达增加。结论:四妙勇安汤能够拮抗Ox-LDL,增加PPARγ表达,降低FABP4水平,使ApoE^(−/−)动脉粥样硬化小鼠颈动脉MMP-2减少,斑块稳定性增加。Objective:To explore the effects of Simiao Yongan(SMYA)Decoction on carotid atherosclerotic plaque in ApoE knockout mice by antagonizing lipid metabolism of oxidation low density lipoprotein(Ox-LDL).Methods:ApoE^(−/−)mice were fed high-fat diet for 2 weeks,then underwent perivascular collar placement(PCCP)and high fat diet for 8 weeks to establish carotid AS plaque model.All mice were divided into 5 groups:sham operation and model groups intragastrically administered with deionized water;treatment groups intragastrically administered with SMYA Decoction,pioglitazone,or atorvastatin for 8 weeks.Automatic biochemical analyzer was used to test total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C),and low density lipoprotein cholesterol(LDL-C)content.The content of ox-LDL in serum was tested by enzyme-linked immunosorbent assay.The pathological changes of carotid artery were observed by hematoxylin-eosin staining and the vasucular parameters were measured.Immunohistochemical method and Western blot assay was used to detect fatty acid binding protein 4(FABP4)and peroxisome proliferator-activated receptorγ(PPARγ)as well as matrix metalloproteinase-2(MMP-2).Results:compared with the sham operation group,HDL-C in serum of the model group was significantly increased(P<0.05);compared with model group,TC and LDL-C levels were significantly increased(P<0.05)while HDL-C was significantly decreased(P<0.05)in SMYA Decoction and atorvastatin groups.In pioglitazone group,LDL-C level was significantly increased(P<0.05)while HDL-C was significantly decreased(P<0.05).Compared with the sham operation group,the ox-LDL content in serum of the model group was increased,and the intima thickness(IT),intima-media thickness(IT/MT),plaque area(PA)as well as lumen area ratio of plaque vessels(PA/LA)were increased(P<0.05).Immunohistochemistry and Western blot results showed that the relative expression of FABP4 and MMP-2 in the model group increased markedly,while the relative expression of PPARγsignificantl

关 键 词：四妙勇安汤 动脉粥样硬化 脂代谢途径 OX-LDL 

分 类 号：R285.5[医药卫生—中药学]