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护肝清脂方饮片汤剂与配方颗粒的化学成分、药效一致性及机制

          研究
                 Δ


          张振华    1, 2* ,龙昌锐 ,吴辉星 ,乡世健 ,周本杰            1, 2 # [1.中山大学药学院(深圳),广东 深圳 518107;2.中山大学
                                    1
                                            1, 2
                            2
          附属第七医院(深圳)药学部,广东 深圳 518107]
          中图分类号  R917;R965      文献标志码  A      文章编号  1001-0408(2025)12-1442-07
          DOI  10.6039/j.issn.1001-0408.2025.12.05

          摘   要  目的  研究护肝清脂方(HGQZ)饮片汤剂与配方颗粒的特征成分含量及对高脂饮食诱导的非酒精性脂肪性肝病
         (NAFLD)模型小鼠药效的一致性,并探讨其潜在作用机制。方法  运用液相色谱-串联三重四极杆质谱技术,分析、比较HGQZ饮
          片汤剂与配方颗粒中 6 种特征成分的含量。将雄性 C57BL/6 小鼠分为正常对照组、模型组、HGQZ 饮片汤剂低/高剂量组(13、26
          g/kg,以生药量计)、HGQZ配方颗粒低/高剂量组(13、26 g/kg,以生药量计),每组6只。除正常对照组小鼠给予普通维持饲料外,
          其余各组小鼠均给予高脂饲料 20 周以建立 NAFLD 模型;造模同时,各组小鼠灌胃相应药液或等体积水 1 次。检测其空腹血糖
         (FBG)水平和葡萄糖、胰岛素耐量,体重和肝指数、白色脂肪指数和棕色脂肪指数,以及脂质指标(总胆固醇、甘油三酯)和肝功能
          指标(天冬氨酸转氨酶、丙氨酸转氨酶)水平,观察其肝组织病理学形态和脂质堆积情况。取模型组、HGQZ饮片汤剂高剂量组、
          HGQZ配方颗粒高剂量组小鼠血清样品,进行代谢组学分析,并针对潜在机制进行验证。结果  HGQZ饮片汤剂与配方颗粒中,人
          参皂苷 Rb1、香蒲新苷、异鼠李素-3-O-新橙皮苷、金丝桃苷、荷叶碱、23-乙酰泽泻醇 B 含量比较,差异均无统计学意义(P>0.05)。
          与模型组比较,HGQZ饮片汤剂组与配方颗粒各剂量组小鼠的肝组织病理改变均有所缓解,炎症细胞浸润和脂肪空泡均有所减
          少,其FBG水平、葡萄糖耐量、胰岛素耐量、体重、肝指数、白色/棕色脂肪指数、脂质和肝功能指标水平均普遍改善(P<0.05),但组
          间比较差异均无统计学意义(P>0.05)。模型组与HGQZ饮片汤剂高剂量组、模型组与HGQZ配方颗粒高剂量组分别有234、136
          个血清差异代谢物,取交集后得共同差异代谢物65种,富集于嘌呤代谢、三羧酸代谢等代谢通路;其中,模型组柠檬酸的含量均显
          著低于HGQZ饮片汤剂和配方颗粒的高剂量组(P<0.05);高剂量的HGQZ饮片汤剂与配方颗粒均可显著升高腺苷一磷酸活化的
          蛋白激酶(AMPK)的磷酸化水平(P<0.05)。结论  HGQZ饮片汤剂和配方颗粒的特征成分含量相当,对NAFLD模型小鼠的改善
          作用相似,且其抗NAFLD作用发挥均与激活AMPK能量代谢通路有关。
          关键词  护肝清脂方;非酒精性脂肪性肝病;饮片汤剂;配方颗粒;一致性研究;含量;药效

          Study  on  chemical  composition,  pharmacodynamic  consistency  and  mechanism  between  Hugan  qingzhi

          formula decoction and its formulated granules
                          1, 2
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                                                                       1, 2
                                           2
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          ZHANG Zhenhua ,LONG Changrui ,WU Huixing ,XIANG Shijian ,ZHOU Benjie [1. School of Pharmacy
         (Shenzhen),  Sun Yat-sen  University,  Guangdong  Shenzhen  518107,  China;2.  Dept.  of  Pharmacy,  the  Seventh
          Affiliated Hospital of Sun Yat-sen University(Shenzhen), Guangdong Shenzhen 518107, China]
          ABSTRACT    OBJECTIVE  To  evaluate  the  contents  of  characteristic  components  in  Hugan  qingzhi  formula (HGQZ)  decoction
          and  formulated  granules  and  the  pharmacodynamic  consistency  of  them  on  high-fat  diet-induced  non-alcoholic  fatty  liver  disease
         (NAFLD)  model  mice,  and  explore  their  potential  underlying  mechanisms  of  action.  METHODS  Liquid  chromatography-tandem
          mass  spectrometry  was  used  to  analyze  and  compare  the  contents  of  six  characteristic  components  in  HGQZ  decoction  and
          formulated  granules.  Male  C57BL/6  mice  were  randomly  divided  into  normal  control  group,  model  group,  HGQZ  decoction  low-
          dose  and  high-dose  groups (13,  26  g/kg,  calculated  by  crude  drugs),  and  HGQZ  formulated  granules  low-dose  and  high-dose
          groups (13, 26 g/kg, calculated by crude drugs), with 6 mice in each group. Except for the normal control group, which was fed
          a regular diet, the mice in the other groups were fed a high-fat diet for 20 weeks to establish the NAFLD model; at the same time,
          the  mice  in  each  group  were  gavaged  with  the  corresponding  drugs/water  once.  The  fasting  blood  glucose (FBG)  levels,  glucose
                                                              and insulin tolerance, body weight, liver index, white adipose
              Δ 基金项目 国家自然科学基金项目(No.82074078);广东省基础
                                                              tissue  index,  brown  adipose  tissue  index,  as  well  as  lipid
          与应用基础研究基金委员会省企联合基金面上项目(No.2022A1515-
                                                              levels  (total  cholesterol,  triglycerides)  and  liver  function
          220027);深圳市科技计划项目(No.ZDSYS20220606100801003)。
             * 第一作者 硕 士 研 究 生 。 研 究 方 向 :中 药 药 理 。 E-mail:    indicators (aspartate  transaminase,  alanine  transaminase)  were
          zhangzhh225@mail2.sysu.edu.cn                       measured.  Additionally,  histopathological  changes  and  lipid
              # 通信作者 主任药师,博士生导师,博士。研究方向:中药活性物                 accumulation  in  liver  tissues  were  observed.  The  serum
          质筛选与药理机制。E-mail:zhoubj23@mail.sysu.edu.cn           samples  of  mice  in  the  model  group,  HGQZ  decoction  high-


          · 1442 ·    China Pharmacy  2025 Vol. 36  No. 12                            中国药房  2025年第36卷第12期
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