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基于巨噬细胞极化探究清热化痰活血方抗动脉粥样硬化的作用

          机制
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          钟华平 ,朱启城 ,邹征伟 ,何正义 ,谢和平 ,陈 旭 ,段志胜 ,肖 天 (1.赣南医科大学第一附属医院心脏
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          中心,江西 赣州 341000;2.赣南医科大学第一附属医院南康院区心血管内科,江西 赣州 341000)
          中图分类号  R965      文献标志码  A      文章编号  1001-0408(2026)04-0438-06
          DOI  10.6039/j.issn.1001-0408.2026.04.05
          摘   要  目的  基于巨噬细胞极化探究清热化痰活血方抗动脉粥样硬化(AS)的作用机制。方法  制备清热化痰活血方含药血清,
          以阿托伐他汀为阳性对照,用以处理RAW264.7巨噬细胞;检测巨噬细胞活性、凋亡率和CD86、CD206的荧光强度以及肿瘤坏死
          因子α(TNF-α)、白细胞介素1β(IL-1β)水平。将喂食高脂饲料的载脂蛋白e基因缺乏(ApoE )小鼠(AS模型小鼠)随机分为模
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          型组、阿托伐他汀组(2.6 mg/kg)及清热化痰活血方低、中、高剂量组(90、180、360 mg/kg),另将喂食普通饲料的C57BL/6J小鼠作
          为正常对照组,每组10只;给药组小鼠灌胃相应药物,每日1次,连续8周。检测各组小鼠血清中TNF-α、IL-1β水平,观察主动脉
          脂质沉积情况(以主动脉整体及根部斑块占比计)和主动脉根部的形态学变化,检测主动脉组织中CD86、CD206表达水平及诱导
          型一氧化氮合酶(iNOS)、精氨酸酶1(Arg-1)、AMP激活蛋白激酶(AMPK)、磷酸化AMPK(p-AMPK)、过氧化物酶体增殖物激活
          受体(PPAR-γ)蛋白表达水平。结果  细胞实验结果显示,5~100 μg/mL清热化痰活血方含药血清能显著提高RAW264.7细胞活
          性(P<0.05),10、50、100 μg/mL 清热化痰活血方含药血清和阿托伐他汀能显著降低 RAW264.7 细胞凋亡率、CD86 荧光强度和
          TNF-α、IL-1β水平,并显著升高CD206荧光强度(P<0.05)。动物实验结果显示,与模型组比较,清热化痰活血方各剂量组和阿托
          伐他汀组小鼠血清中TNF-α、IL-1β水平,主动脉整体及根部斑块占比,CD86表达和iNOS蛋白表达均显著降低/下调,而CD206表
          达和Arg-1、PPAR-γ蛋白表达以及AMPK磷酸化表达均显著上调(P<0.05);主动脉病理形态均有不同程度改善。结论  清热化痰
          活血方可通过调控巨噬细胞极化,增加M2型巨噬细胞比例,进而有效抑制AS斑块形成、减轻炎症反应,发挥抗AS的作用。
          关键词  清热化痰活血方;巨噬细胞极化;动脉粥样硬化;AMPK/PPAR-γ信号通路

          Mechanism  of  action  of  Qingre  huatan  huoxue  decoction  against  atherosclerosis  based  on  macrophage
          polarization
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          ZHONG Huaping ,ZHU Qicheng ,ZOU Zhengwei ,HE Zhengyi ,XIE Heping ,CHEN Xu ,DUAN Zhisheng ,
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          XIAO Tian(1.  Heart  Center,  the  First  Affiliated  Hospital  of  Gannan  Medical  University,  Jiangxi  Ganzhou
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          341000,  China;2.  Dept.  of  Cardiovascular  Medicine,  Nankang  Campus  of  the  First  Affiliated  Hospital  of
          Gannan Medical University, Jiangxi Ganzhou 341000, China)
          ABSTRACT    OBJECTIVE  To explore the mechanism of action of Qingre huatan huoxue decoction against atherosclerosis (AS)
          based  on  macrophage  polarization.  METHODS  Using  atorvastatin  served  as  the  positive  control,  the  drug-containing  serum  of  the
          Qingre  huatan  huoxue  decoction  was  prepared  to  treat  RAW264.7  macrophages.  Macrophage  viability,  apoptosis  rate,  and  the
          fluorescence  intensities  of  CD86  and  CD206  were  measured,  along  with  the  levels  of  tumor  necrosis  factor- α (TNF- α)  and
          interleukin-1β (IL-1β).  Apolipoprotein  E-deficient (ApoE -/- )  mice (AS  model  mice)  fed  with  a  high-fat  diet  were  randomly
          assigned  to  model  group,  atorvastatin  group (2.6  mg/kg),  and  low- ,  medium-  and  high-dose  groups  of  Qingre  huatan  huoxue
          decoction (90,  180,  360  mg/kg),  respectively.  C57BL/6J  mice  fed  with  a  standard  diet  served  as  the  normal  control  group,  with
          10  mice  per  group.  The  treatment  group  mice  were  administered  the  corresponding  drugs  intragastrically,  once  daily,  for  8
          consecutive  weeks.  Serum  levels  of TNF-α  and  IL-1β  were  measured  in  all  groups.  Lipid  deposition  in  the  aorta (assessed  by  the
          percentage  of  plaque  in  the  entire  aorta  and  aortic  root)  and  morphological  changes  in  the  aortic  root  were  observed.  Expression
          levels  of  CD86  and  CD206  in  aortic  tissue,  as  well  as  the  protein  expression  levels  of  inducible  nitric  oxide  synthase (iNOS),
          arginase-1 (Arg-1),  AMP-activated  protein  kinase (AMPK),  phosphorylated  AMPK (p-AMPK),  and  peroxisome  proliferator-
                                                              activated  receptor  γ (PPAR- γ)  in  aortic  tissues  were  all
              Δ 基金项目 江西省教育厅科学技术研究项目(No.GJJ2201440)
             *第一作者 主治医师,硕士。研究方向:心血管疾病基础与临床。                   detected.  RESULTS  Cell  experiment  results  showed  that,  at
          E-mail:zhonghuaphp@163.com                          concentrations  of  5-100  μg/mL,  the  drug-containing  serum  of
              # 通信作者 副主任医师。研究方向:心血管内科疾病诊治。                    the  Qingre  huatan  huoxue  decoction  significantly  increased
          E-mail:xlz123xlz123@163.com                         RAW264.7  cell  viability  (P<0.05).  The  drug-containing


          · 438 ·    China Pharmacy  2026 Vol. 37  No. 4                               中国药房  2026年第37卷第4期
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