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健脾化痰方调控 HMGB1/RAGE 通路改善大鼠多囊卵巢综合征

          的机制研究
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          徐 静 ,向 英(湖北省中医院光谷院区妇产科/中医肝肾研究及应用湖北省重点实验室,武汉 430070)
          中图分类号  R965      文献标志码  A      文章编号  1001-0408(2026)08-1009-06
          DOI  10.6039/j.issn.1001-0408.2026.08.07

          摘  要  目的  探究健脾化痰方(JPHTF)调控高迁移率族蛋白B1(HMGB1)/晚期糖基化终末产物受体(RAGE)信号通路对多囊卵
          巢综合征(PCOS)大鼠的影响。方法  将大鼠随机分为正常(Con)组、PCOS组、JPHTF低剂量(JPHTF-L,5.54 g/kg)组、JPHTF高剂
          量(JPHTF-H,11.07g/kg)组、JPHTF-H+重组HMGB1蛋白(JPHTF 11.07 g/kg+rHMGB1 8 μg/kg)组和二甲双胍(0.27 g/kg)组,每组
          12只。除Con组大鼠以1%羧甲基纤维素钠溶液灌胃,同时喂食普通饲料外,其余大鼠通过高脂饮食联合来曲唑制备PCOS模型。
          造模成功后,各给药组大鼠灌胃/尾静脉注射相应药物,每日1次,连续4周。干预结束24 h后,称量大鼠体重,计算卵巢系数,检测
          空腹血糖(FBG)和血清中空腹胰岛素(FINS)、促卵泡素(FSH)、黄体生成素(LH)、睾酮(T)、雌二醇(E2 )水平,计算胰岛素抵抗稳
          态模型评估指数,以及检测卵巢组织中肿瘤坏死因子α(TNF-α)、白细胞介素18(IL-18)、IL-1β水平和HMGB1、RAGE、磷酸化核
          因子 κB(p-NF-κB)和 NF-κB 蛋白表达水平,观察卵巢组织形态及囊性卵泡和黄体数量。结果  与 PCOS 组比较,JPHTF-L 组、
          JPHTF-H 组和二甲双胍组大鼠卵巢组织多囊性病变均有不同程度改善;体重,卵巢系数,FBG,囊性卵泡数量,血清中 FINS、
          HOMA-IR、T、LH、LH/FSH水平,卵巢组织中TNF-α、IL-18、IL-1β水平和HMGB1、RAGE蛋白表达水平以及NF-κB蛋白磷酸化水
          平均显著降低;黄体数量和血清中E2、FSH水平均显著升高(P<0.05)。与JPHTF-H组比较,JPHTF-H+rHMGB1组大鼠上述指标
          变化均显著逆转(P<0.05)。结论  JPHTF可通过抑制HMGB1/RAGE信号通路来降低PCOS大鼠炎症反应,减轻卵巢损伤,调节
          激素平衡,改善胰岛素抵抗和卵泡发育。
          关键词  健脾化痰方;多囊卵巢综合征;HMGB1/RAGE信号通路;胰岛素抵抗;卵泡发育;炎症反应

          Mechanism  of  Jianpi  huatan  formula  improving  polycystic  ovary  syndrome  in  rats  by  regulating  the
          HMGB1/RAGE signaling pathway
          XU Jing,XIANG Ying(Dept.  of  Obstetrics  and  Gynecology,  Guanggu  Branch,  Hubei  Provincial  Hospital  of
          TCM/Hubei  Provincial  Key  Laboratory  of  Research  and  Application  of  TCM  for  Liver  and  Kidney  Diseases,
          Wuhan 430070, China)

          ABSTRACT   OBJECTIVE  To explore the effects of the Jianpi huatan formula (JPHTF) on polycystic ovary syndrome (PCOS)
          in  rats  by  regulating  the  high  mobility  group  box  1  protein (HMGB1)/receptor  for  advanced  glycation  end  products (RAGE)
          signaling  pathway.  METHODS  The  rats  were  randomly  divided  into  the  normal (Con)  group,  the  PCOS  group,  the  JPHTF-L
          group (5.54  g/kg),  the  JPHTF-H  group (11.07  g/kg),  the  JPHTF-H+rHMGB1  group (11.07  g/kg  of  JPHTF+8  μg/kg  of
          rHMGB1), and metformin group (0.27 g/kg), with 12 rats in each group. Except for the rats of Con group, which were given 1%
          sodium  carboxymethyl  cellulose  intragastrically  and  fed  with  normal  chow,  the  remaining  rats  were  induced  to  develop  PCOS
          models by using a high-fat diet combined with letrozole. After successful modeling, rats in each drug group were administered the
          corresponding  drugs  by  gavage  or  tail  vein  injection  once  a  day  for  4  consecutive  weeks.  24  h  after  the  intervention,  body  weight
          and ovarian coefficient were detected. The levels of fasting blood glucose (FBG), serum levels of fasting insulin (FINS), follicle
          stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T) and estradiol (E2 ) were detected. The homeostasis model
          assessment  of  insulin  resistance (HOMA-IR)  was  calculated.  The  levels  of  tumor  necrosis  factor-α (TNF-α),  interleukin-18 (IL-
          18)  and  IL-1β  and  the  protein  expressions  of  HMGB1,  RAGE,  phosphorylated  nuclear  factor-κB (p-NF-κB)  and  NF-κB  in  the
          ovarian  tissues  of  rats  were  detected.  The  morphology  of  ovarian  tissue  was  observed,  and  the  numbers  of  cystic  follicles  and
          corpora  lutea  were  counted.  RESULTS  Compared  with  PCOS  group,  polycystic  changes  of  ovarian  tissue  in  rats  showed  varying
                                                             degrees  of  improvement  in  the  JPHTF-L  group,  JPHTF-H
             Δ 基金项目 湖北省自然科学基金项目(No.2023AFD180)               group,  and  metformin  group;  body  weight,  ovarian
             *第一作者 主治医师,硕士。研究方向:中医妇科。E-mail:
                                                             coefficient,  FBG,  the  number  of  cystic  follicles,  serum  levels
          196435986@qq.com
             # 通信作者 主任医师,硕士。研究方向:中医妇科。E-mail:                of FINS, HOMA-IR, T, LH, LH/FSH, the levels of TNF-α,
          delhv8@163.com                                     IL-18  and  IL-1β  and  protein  expressions  of  HMGB1  and


          中国药房  2026年第37卷第8期                                                China Pharmacy  2026 Vol. 37  No. 8    · 1009 ·
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