心痛泰颗粒对动脉粥样硬化ApoE^(−/−)小鼠ox-LDL、ICAM-1和VCAM-1表达的影响  

Effects of Xin-Tong-Tai granule on expression of ox-LDL,ICAM-1 and VCAM-1 in ApoE^(−/−)mice with atherosclerosis

作　　者：曾清华 尹紫薇 黄爱思 陈景怡 郭志华 魏佳明 ZENG Qinghua;YIN Ziwei;HUANG Aisi;CHEN Jingyi;GUO Zhihua;WEI Jiaming(School of Traditional Chinese Medicine,Hunan University of Chinese Medicine,Hunan Provincical Key Laboratory of TCM Intelligent Diagnosis and Prevention of Chronic Diseases,Internet Plus Postgraduate Joint Training Base for Intelligent Application of Traditional Chinese Medicine Diagnosis and Treatment of Chronic Diseases and Health Preservation,Changsha 410208,China)

机构地区：[1]湖南中医药大学中医学院,慢病中医智能诊断与治未病湖南省普通高等学校重点实验室,互联网+慢病中医诊治与养生智能化应用研究生联合培养基地,湖南长沙410208

出　　处：《中国病理生理杂志》2024年第6期989-996,共8页Chinese Journal of Pathophysiology

基　　金：湖南省自然科学基金项目(No.2021JJ30492);湖南中医药大学中医学一流学科重点项目(No.2021ZYX14);湖南省研究生科研创新项目(No.2022CX133,No.2023CX178);湖南中医药大学“一方”研究生创新项目(No.2022YF05);湖南省中医药科研项目重点课题(No.2021029);湖南省教育厅科研项目重点课题(No.20A384)。

摘　　要：目的:探讨心痛泰颗粒对动脉粥样硬化ApoE^(−/−)小鼠氧化型低密度脂蛋白(ox-LDL)、细胞间黏附分子1(ICAM-1)和血管细胞黏附分子1(VCAM-1)表达的影响及其机制。方法:6~8周龄SPF级健康雄性ApoE^(−/−)小鼠72只,采用高脂饮食喂养12周进行造模,另设SPF级健康雄性C57BL/6J野生小鼠12只为对照组,予以普通饲料喂养。各组相应药物给药8周后,观察各组小鼠体质量及一般情况,采用生化试剂盒检测小鼠血清中总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C)含量,HE染色和油红O染色观察主动脉病理结构,ELISA法检测血清ox-LDL及主动脉组织中ICAM-1和VCAM-1水平,Western blot法检测主动脉NADPH氧化酶4(NOX4)、NOX亚单位p22phox、核因子抑制蛋白激酶α(IKK-α)、IKK-β和核因子κB(NF-κB)蛋白表达情况。结果:与对照组比较,模型组小鼠体质量增加(P<0.05),且毛发晦暗无光泽、局部脱落,抓起反应迟钝;血清TC、TG和LDL-C上升,HDL-C下降(P<0.05),血清ox-LDL水平上升(P<0.05),主动脉ICAM-1和VCAM-1水平升高(P<0.05),主动脉NOX4、p22phox、IKK-α、IKK-β和NF-κB蛋白表达增加(P<0.05)。与模型组比较,各用药组小鼠体质量下降(P<0.05),且毛发脱落及反应灵活程度亦有所改善;血清TC、TG和LDL-C降低,HDL-C升高(P<0.05),血清ox-LDL水平下降(P<0.05),主动脉ICAM-1和VCAM-1水平降低(P<0.05),主动脉NOX4、p22phox、IKK-α、IKK-β和NF-κB蛋白表达减少(P<0.05)。HE及油红O染色显示,模型组小鼠血管内可见典型动脉粥样硬化斑块,且红染区域分布广泛;各用药组与模型组比较,以上情况均有不同程度减轻。结论:心痛泰颗粒可减少高脂饮食诱导的ApoE^(−/−)小鼠动脉粥样硬化斑块面积,下调血清TC、TG和LDL-C水平,升高HDL-C水平,减少血清ox-LDL水平,下调主动脉ICAM-1和VCAM-1水平,抑制主动脉NOX4、p22phox、IKK-α、IKK-β和NF-κB蛋白的表达,改善动脉�AIM:To investigate the effects and mechanism of Xin-Tong-Tai granule on oxidized low-density lipoprotein(ox-LDL),intercellular adhesion molecule-1(ICAM-1)and vascular cell adhesion molecule-1(VCAM-1)in ApoE^(−/−)mice with atherosclerosis(AS).METHODS:A total of 72 SPF-grade healthy male ApoE^(−/−)mice aged 6~8 weeks were fed with high-fat diet for 12 weeks to replicate AS models,and 12 SPF-grade healthy male C57BL/6J wild mice were fed with ordinary diet as the control group.After the corresponding drugs were administered for 8 weeks,the body weight and general condition of mice in each group were observed.The serum levels of total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C)and low-density lipoprotein cholesterol(LDL-C)were detected by biochemical kits.The pathological structures of aorta were observed by HE and oil red O staining.The levels of serum ox-LDL and aortic ICAM-1 and VCAM-1 were detected by ELISA.The protein levels of NADPH oxidase 4(NOX4),NOX subunit p22phox,inhibitor ofκB kinase-α(IKK-α),IKK-βand nuclear factor-κB(NF-κB)in aorta were detected by Western blot.RESULTS:Compared with control group,the mice in model group showed increased body weight(P<0.05),dull and local shedding hair,slow grasping response,increased serum TC,TG and LDL-C levels,decreased serum HDL-C level(P<0.05),increased the levels of serum ox-LDL and aortic ICAM-1 and VCAM-1(P<0.05),and increased protein expressions of NOX4,p22phox,IKK-α,IKK-βand NF-κB in aorta(P<0.05).Compared with model group,the body weight of mice in each treatment group decreased(P<0.05),the hair loss and the response flexibility were also improved.The serum levels of TC,TG and LDL-C decreased and HDL-C increased(P<0.05).The levels of serum ox-LDL and aortic ICAM-1(except the low-dose Xin-Tong-Tai granule group)and VCAM-1 decreased(P<0.05).The protein levels of NOX4,p22phox,IKK-α,IKK-βand NF-κB in aorta decreased(P<0.05).HE and oil red O staining showed that typical AS plaques could be seen in blood vessels o

关 键 词：动脉粥样硬化 心痛泰颗粒 氧化型低密度脂蛋白 细胞间黏附分子1 血管细胞黏附分子1 

分 类 号：R363.2[医药卫生—病理学] R285.5[医药卫生—基础医学] R543