新型补骨脂素PAP-1对大鼠动脉粥样硬化的影响及心脏保护作用  

Effects of PAP-1 on Atherosclerosis and Cardioprotection in Rats

作　　者：缪玉影 戴雨晨 桑明 沈月红[3] 沈旭[1] 曹鹏[4] 周谦[5] MIAO Yu-ying;DAI Yu-chen;SANG Ming;SHEN Yue-hong;SHEN Xu;CAO Peng;ZHOU Qian(School of Medicine&Holistic Integrative Medicine,Nanjing University of Chinese Medicine,Nanjing,210023,China;Laboratory of Cellular and Molecular Biology,Jiangsu Province Academy of Traditional Chinese Medicine,Nanjing,210028,China;The Third Clinical Medical College,Nanjing University of Chinese Medicine,Nanjing,210028,China;College of Pharmacy,Nanjing University of Chinese Medicine,Nanjing,210023,China;Integrated Traditional Chinese and Western Medicine Hospital Affiliated to Nanjing University of Chinese Medicine,Nanjing,210028,China)

机构地区：[1]南京中医药大学医学院·整合医学学院,江苏南京210023 [2]江苏省中医药研究院细胞与分子生物学实验室,江苏南京210028 [3]南京中医药大学第三临床医学院,江苏南京210028 [4]南京中医药大学药学院,江苏南京210023 [5]南京中医药大学附属中西医结合医院,江苏南京210028

出　　处：《南京中医药大学学报》2021年第4期535-541,共7页Journal of Nanjing University of Traditional Chinese Medicine

基　　金：南京中医药大学中药学一流学科开放课题(2020YLXK024)。

摘　　要：目的探讨5-(4-苯氧基丁氧基)补骨脂素(PAP-1)对大鼠动脉粥样硬化(AS)的影响及心脏保护作用。方法建立AS大鼠模型,随机分为对照组、模型组、PAP-1组和阿托伐他汀(AV)阳性药组。HE染色观察颈动脉形态学改变,Western blot法检测巨噬细胞清道夫受体1(MSR1)和ATP结合盒转运体A1(ABCA1)蛋白表达,COD-PAP酶法检测血清总胆固醇(CHO)含量,ELISA法测定血清炎症因子TNF-α、IL-6和IL-1β含量,麦胚凝集素(WGA)染色测量心肌细胞面积,Vevo 3100高分辨动物超声影像系统观察各组大鼠左心室形态并计算心功能,Masson和免疫组织化学法检查心肌组织纤维化程度。结果PAP-1可以降低AS大鼠血清CHO含量和炎症因子TNF-α、IL-6和IL-1β的水平;下调AS大鼠颈主动脉MSR1,上调ABCA1蛋白表达;减轻AS大鼠颈主动脉管壁增厚。此外,PAP-1可以抑制AS大鼠心肌细胞面积增大和心室壁增厚,减轻心肌组织纤维化程度。结论PAP-1对AS大鼠具有一定保护作用,可能与降低血清血脂和炎症因子水平,调控MSR1和ABCA1蛋白表达有关。PAP-1还对AS大鼠心脏具有保护作用,表现为改善AS大鼠心脏结构和功能异常,抑制心肌纤维化等。OBJECTIVE To explore the effect of 5-(4-phenoxybutoxy)psoralen(PAP-1)on atherosclerosis(AS)and cardioprotection in rats.METHODS The AS model was established in rats,and the rats were randomly divided into control,model,PAP-1 and AV groups.HE staining was used to observe the carotid artery morphology.Western blot was performed to detect the expressions of MSR1 and ABCA1.Serum total cholesterol(CHO)was determined by COD-PAP enzymatic method.ELISA method was used to measure the levels of inflammatory cytokines TNF-α,IL-1βand IL-6.The cardiomyocyte areas were evaluated by WGA staining.Vevo 3100 doppler echocardiography was used to observe ventricular ultrasound images and calculate cardiac function.The levels of cardiomyocyte fibrosis and collagen deposition were detected by Masson and immunohistochemical staining.RESULTS PAP-1 intervention reduced the levels of serum CHO and inflammatory cytokines TNF-α,IL-1βand IL-6.PAP-1 reversed the protein expressions of MSR1 and ABCA1.PAP-1 inhibited cardiac enlargement and structural remodeling,and reduced cardiomyocyte fibrosis accumulation.CONCLUSION PAP-1 has a certain role in AS rats,which may be related to the regulation of the expression of MSR1 and ABCA1 and reduction of serum CHO.PAP-1 also has a cardioprotection effect on AS rats via alleviation of cardiac structure enlargement,function disorder and fibrosis.

关 键 词：5-(4-苯氧基丁氧基)补骨脂素 动脉粥样硬化 心脏保护 

分 类 号：R285.5[医药卫生—中药学]