黄芩苷对AngⅡ诱导的病理性左心室重塑的干预效应和机制研究  

Effects and Mechanisms of Baicalin on Angiotensin Ⅱ-Induced Pathological Left Ventricular Remodeling

作　　者：薛聿杰 崔艺萌 李蒙丽 崔金刚[1,2] 陈瑜[1,2] 张腾[1,2] XUE Yujie;CUI Yimeng;LI Mengli;CUI Jingang;CHEN Yu;ZHANG Teng(Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 200437,China;Clinical Research Institute of Integrative Medicine,Shanghai Academy of Traditional Chinese Medicine,Shanghai 200437,China)

机构地区：[1]上海中医药大学附属岳阳中西医结合医院,上海200437 [2]上海市中医药研究院中西医结合临床研究所,上海200437

出　　处：《世界科学技术-中医药现代化》2024年第10期2703-2715,共13页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：国家自然科学基金委员会面上项目(82074049):人参皂苷Rb1抗心肌肥大的免疫相关-外泌体源性-非编码RNA调控机制研究,负责人:张腾;上海市卫生健康委员会、上海市中医药发展办公室上海市进一步加快中医药事业发展三年行动计划(ZY(2018-2020)-CCCX-2004-07):中医药防治高血压及靶器官损伤的优势效应机制研究,负责人:张腾。

摘　　要：目的探讨黄芩苷对病理性左心室重塑的干预效应和机制。方法体内实验:采用血管紧张素Ⅱ(AngiotensinⅡ,AngⅡ)诱导病理性左心室重塑小鼠模型,探讨黄芩苷对病理性左心室重塑的干预效应。将C57BL/6J小鼠随机分为5组:假手术组,模型组(AngⅡ组),黄芩苷低、中、高剂量给药组。除Sham组外,其余各组予AngⅡ持续输注2周,各给药组分别给予相应剂量黄芩苷灌胃,连续干预2周。测量小鼠血压、体质量、心脏重量和胫骨长度;采用小麦胚芽凝集素(Wheat germ agglutinin,WGA)免疫组织化学染色测量心肌细胞横截面积;对心肌细胞心房钠尿肽(Atrial natriuretic peptide,ANP)的表达进行分析;采用苏木素-伊红(Hematoxylin-eosin,HE)、Masson’s trichrome染色观察心脏病理改变。体外实验:采用AngⅡ诱导心肌细胞肥大模型,明确黄芩苷是否对心肌肥大具有直接的干预作用。将H9C2心肌细胞分为溶剂对照组(VC组)、模型组(AngⅡ组)、给药组(Bai组)。采用罗丹明-鬼笔环肽染色对心肌细胞大小进行评估;采用免疫荧光染色对心肌细胞ANP水平进行分析;采用线粒体超氧化物(Mito-SOX)染色对线粒体氧化应激水平进行分析;采用线粒体膜电位检测试剂盒(JC-1)对细胞线粒体膜电位(ΔΨm)进行分析;采用钙黄绿素乙酰甲酯(Calcein AM)染色对细胞线粒体通透性转换孔(mPTP)的开放程度进行评估。结果体内实验:中、高剂量的黄芩苷可显著拮抗AngⅡ诱导的小鼠的收缩压升高(P<0.05);黄芩苷显著抑制AngⅡ输注小鼠的心脏重量和胫骨长度的比率(HW/TL)及心脏重量和体质量的比率(HW/BW)的升高;黄芩苷显著抑制AngⅡ输注小鼠的心肌细胞横截面积和ANP水平(P<0.05);黄芩苷显著抑制AngⅡ诱导的炎症和纤维化(P<0.05)。体外实验:黄芩苷显著抑制AngⅡ诱导的心肌细胞肥大和心肌细胞内ANP水平的增加(P<0.05);黄芩苷显著抑制AngⅡ诱导的心肌细胞线粒体氧化�Objective The current study aims to investigate the protective effect and mechanisms of baicalin on pathological left ventricular remodeling.Methods Angiotensin Ⅱ(Ang Ⅱ)infusion mouse model was adopted to evaluate the impact of baicalin on pathological left ventricular remodeling in vivo.C57BL/6J mice were randomly allocated to 5 experimental groups,including sham controls,model group(Ang Ⅱ-infusion controls),as well as low-,medium-,and high-dose baicalin treatment groups.Except for the sham controls,C57/BL6 mice were subjected to Ang Ⅱ infusion for 2 weeks.The mice from the baicalin treatment groups received baicalin via gavage at the indicated doses for 2 weeks.The blood pressure,body weight,heart weight and tibia length were measured at the end of the indicated treatments.Immunohistochemistry of wheat germ agglutinin(WGA)was performed to examine the cross-sectional area of cardiomyocytes.Immunohistochemistry was also performed to assess the expression of atrial natriuretic peptide(ANP)in cardiomyocytes.Hematoxylin/eosin(HE)staining and Masson's trichrome staining were performed to evaluate the cardiac pathologies.In vitro experiments were as follows.Ang Ⅱ was adopted to induce cardiomyocyte hypertrophy in H9C2 cells in order to determine if baicalin is able to directly suppress cardiomyocyte hypertrophy.H9C2 cells were divided into vehicle control group(VC group),model group(Ang Ⅱ group)and baicalin group(Bai group).The morphology and size of cardiomyocytes were examined by rhodamine phalloidin staining.The intracellular level of ANP was analyze by immunofluorescence staining.Mitochondrial superoxide(Mito-SOX)was assessed to evaluate oxidative stress.The mitochondrial membrane potential(ΔΨm)was analyzed by JC-1 staining.The opening of mitochondrial permeability transition pore(mPTP)was evaluated by calcein acetyl methyl ester(Calcein AM)staining.Results The in vivo findings:Baicalin significantly antagonized Ang Ⅱ-induced elevation of systolic blood pressure(P<0.05)when administered at the medi

关 键 词：黄芩苷 心肌肥大 左心室重塑 AngⅡ 线粒体功能障碍 

分 类 号：R285.5[医药卫生—中药学]