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小白薇不同萃取物对非酒精性脂肪性肝炎的改善作用及机制
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          乔 雪 ,李欣坪,薛咏梅,方琼莲,王蒙蒙,林玉萍(云南中医药大学中药学院/云南省南药可持续利用重点实验
                                                       #
                *
          室,昆明 650500)


          中图分类号  R965      文献标志码  A      文章编号  1001-0408(2023)10-1182-05
          DOI  10.6039/j.issn.1001-0408.2023.10.06

          摘   要  目的  探讨小白薇不同萃取物对非酒精性脂肪性肝炎(NASH)的改善作用和作用机制。方法  用游离脂肪酸诱导人正常
          肝细胞LO2脂肪变性,实验分为正常组、模型组、水飞蓟宾组(100 μmol/mL)、小白薇乙醇萃取物(TYS)组(50 μg/mL)、小白薇乙
          酸乙酯萃取物(TYSA)组(50 μg/mL)、小白薇正丁醇萃取物(TYSB)组(50 μg/mL),药物干预24 h后观察各组LO2细胞内的脂滴
          沉积情况,检测细胞内总胆固醇(TC)、三酰甘油(TG)、丙二醛(MDA)、谷胱甘肽(GSH)含量和天冬氨酸转氨酶(AST)、丙氨酸转
          氨酶(ALT)、超氧化物歧化酶(SOD)活性以及Kelch样环氧氯丙烷相关蛋白1(Keap1)、核因子E2相关因子2(Nrf2)、血红素氧合酶1
         (HO-1)mRNA表达水平。用高脂饮食诱导建立NASH大鼠模型,实验分为正常组、模型组、水飞蓟宾组(12.6 mg/kg)、TYS组(80
          mg/kg)、TYSA组(80 mg/kg)、TYSB组(80 mg/kg),每组6只。药物干预6周后计算各组大鼠的肝脏指数,观察肝脏病理形态变化,
          检测血清中 TC、TG、HDL-C、LDL-C 含量和 AST、ALT 活性以及肝组织中 MDA、GSH 含量和 SOD 活性。结果  与模型组比较,
          TYS、TYSA、TYSB 可降低 LO2 细胞脂肪变性后的脂滴沉积和细胞内 TC、TG、MDA 含量以及 AST、ALT 活性,升高 SOD 活性、
          GSH含量和Keap1、Nrf2、HO-1 mRNA表达水平,部分差异有统计学意义(P<0.05);还可显著改善NASH模型大鼠的肝损伤,降
          低其肝脏指数和TC、TG、LDL-C、MDA含量以及AST、ALT活性,升高HDL-C(TYS、TYSB除外)、GSH含量和SOD活性,以TYSA
          效果最明显(P<0.05)。结论  TYS、TYSA、TYSB对NASH具有一定的改善作用,其中TYSA效果最明显;其作用机制可能与上调
          Keap1/Nrf2/HO-1信号通路,抑制氧化应激有关。
          关键词  小白薇;非酒精性脂肪性肝炎;游离脂肪酸;正常肝细胞LO2;肝功能;抗氧化活性;大鼠

          Improvement  effect  and  mechanism  of  different  extracts  from  Tylophora  yunnanensis  on  non-alcoholic
          steatohepatitis
          QIAO Xue,LI Xinping,XUE Yongmei,FANG Qionglian,WANG Mengmeng,LIN Yuping(School  of  Chinese
          Materia  Medica/Yunnan  Key  Laboratory  of  Southern  Medicinal  Resource,  Yunnan  University  of  Chinese
          Medicine, Kunming 650500, China)

          ABSTRACT      OBJECTIVE  To  investigate  the  improvement  effect  and  mechanism  of  different  extracts  from  Tylophora
          yunnanensis on non-alcoholic steatohepatitis (NASH). METHODS Normal human liver LO2 cells were induced to steatosis by free
          fatty acid, then were divided into normal group, model group, silybin group (100 μmol/mL), T. yunnanensis ethanol extracts
         (TYS)  group (50  μg/mL),  T.  yunnanensis  ethyl  acetate  extracts (TYSA)  group (50  μg/mL),  and  T.  yunnanensis  n-butanol
          extracts (TYSB)  group (50  μg/mL). After  24  hours  of  drug  intervention,  the  deposition  of  lipid  droplets  was  observed  in  LO2
          cells  in  each  group.  The  contents  of  total  cholesterol (TC),  triacylglycerol (TG),  malondialdehyde (MDA)  and  glutathione
         (GSH), the activities of aspartate transaminase (AST), alanine transaminase (ALT) and superoxide dismutase (SOD), the mRNA
          expressions of Kelch-like ECH-associated protein 1 (Keap1), nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-
          1)  were  detected.  NASH  rat  model  was  induced  by  a  high-fat  diet,  and  then  divided  into  normal  group,  model  group,  silybin
          group (12.6 mg/kg), TYS group (80 mg/kg), TYSA group (80 mg/kg) and TYSB group (80 mg/kg), with six rats in each group.
          The liver indexes of rats in each group were calculated after 6 weeks of drug intervention. The liver histopathological changes were
          observed,  and  the  contents  of TC, TG,  HDL-C  and  LDL-C, AST  and ALT  activities  in  serum,  the  contents  of  MDA  and  GSH,
          SOD  activities  in  liver  tissue  were  detected.  RESULTS  Compared  with  model  group,  TYS,  TYSA  and  TYSB  could  reduce  lipid
          droplet  deposition,  intracellular  TC,  TG  and  MDA  contents, AST  and ALT  activities,  and  increase  SOD  activity,  GSH  content,
          and  Keap1,  Nrf2,  HO-1  mRNA  expression  levels  in  LO2  cells  after  steatosis  to  varying  degrees,  with  some  differences  being
                                                              statistically  significant  (P<0.05).  They  also  significantly
              Δ 基金项目 国家自然科学基金资助项目(No.82160781);云南省
                                                              improved  liver  injury  in  NASH  model  rats,  reduced  their  liver
          应用基础研究项目-中医联合专项面上项目(No.202001AZ07000
                                                              indexes,  TC,  TG,  LDL-C  and  MDA  contents, AST  and ALT
          1-042)
                                                              activities, and increased HDL-C (except for TYS and TYSB),
             *第一作者 硕士研究生。研究方向:中药质量控制。E-mail:
          1208734974@qq.com                                   GSH  contents  and  SOD  activity,  with  TYSA  having  the  most
              # 通信作者 教授,硕士生导师,硕士。研究方向:中药或天然药物                 significant  effect (P<0.05).  CONCLUSIONS  TYS,  TYSA
          活性成分。E-mail:11217005@qq.com                         and  TYSB  have  a  certain  improvement  effect  on  NASH,


          · 1182 ·    China Pharmacy  2023 Vol. 34  No. 10                            中国药房  2023年第34卷第10期
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