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隐丹参酮调节SDF-1/CXCR4轴对卵巢功能不全大鼠的保护作用
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          瞿 谆 ,马惠荣 ,冯 丹 ,丑 丹 ,张 喻 ,李红梅(1.武汉市中医医院妇科,武汉 430014;2.河北中医
                 1*
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                                    1
                                                    1
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          大学中医妇科教研室,石家庄 050020)
          中图分类号  R965;R711.5      文献标志码  A      文章编号  1001-0408(2024)24-2998-06
          DOI  10.6039/j.issn.1001-0408.2024.24.06
          摘   要  目的  基于基质细胞衍生因子1(SDF-1)/趋化因子CXC亚家族受体4(CXCR4)轴,探究隐丹参酮对卵巢功能不全(POI)
          大鼠的保护作用及潜在机制。方法  采用腹腔注射乙烯基环己烯(VCD)的方法建立POI大鼠模型,并将造模成功的大鼠分为模型
          组、隐丹参酮低剂量组(50 mg/kg)、隐丹参酮高剂量组(100 mg/kg)、隐丹参酮高剂量+AMD3100组(100 mg/kg隐丹参酮+2.5 mg/kg
          CXCR4抑制剂AMD3100),每组10只;另取大鼠10只,以生理盐水代替VCD注射,作为对照组。各药物组大鼠灌胃或(和)腹腔
          注射相应药液,每天1次,连续4周。检测各组大鼠血清中雌二醇(E2 )、黄体生成素(LH)、卵泡刺激素(FSH)水平和卵巢组织中活
          性氧(ROS)、丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)水平,观察其卵巢组织形态,检测其卵巢组
          织细胞凋亡情况以及其中 SDF-1、CXCR4 mRNA 和胱天蛋白酶 3(caspase-3)、B 细胞淋巴瘤 2(Bcl-2)、Bcl-2 关联 X 蛋白(Bax)、
          SDF-1、CXCR4蛋白的表达情况。结果  与对照组比较,模型组大鼠卵巢萎缩,原始卵泡数量减少,闭锁卵泡数量增多,损伤明显;
          其血清中E2水平,卵巢组织中SOD、GSH-Px水平,以及卵巢组织中SDF-1、CXCR4 mRNA的表达和Bcl-2、SDF-1、CXCR4蛋白的
          表达均显著降低或下调;血清中FSH和LH水平,卵巢组织中ROS和MDA水平,细胞凋亡率,以及卵巢组织中caspase-3、Bax蛋白
          的表达均显著升高或上调(P<0.05)。与模型组比较,隐丹参酮低、高剂量组大鼠卵巢组织病变明显好转,各定量指标均显著改善
         (P<0.05);AMD3100可显著逆转隐丹参酮对上述指标的改善作用(P<0.05)。结论  隐丹参酮可通过激活SDF-1/CXCR4轴来减
          少POI大鼠卵巢组织细胞凋亡,减轻氧化应激,调节血清激素水平,进而改善卵巢损伤。
          关键词  隐丹参酮;卵巢功能不全;氧化应激;激素;SDF-1/CXCR4轴

          Protective  effect  of  cryptotanshinone  on  premature  ovarian  insufficiency  rats  by  regulating  the  SDF-1/
          CXCR4 axis
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          QU Zhun ,MA Huirong ,FENG Dan ,CHOU Dan ,ZHANG Yu ,LI Hongmei(1. Dept. of Gynecology, Wuhan
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          Hospital  of  Traditional  Chinese  Medicine,  Wuhan  430014,  China;2.  Dept.  of  Traditional  Chinese  Medicine
          Gynecology, Hebei University of Chinese Medicine, Shijiazhuang 050020, China)
          ABSTRACT    OBJECTIVE To investigate the protective effect of cryptotanshinone on premature ovarian insufficiency (POI) rats
          and its potential mechanism based on stromal cell-derived factor-1 (SDF-1)/CXC subfamily receptor 4 (CXCR4) axis. METHODS
          POI  rat  model  was  established  by  intraperitoneal  injection  of  vinylcyclohexene (VCD).  The  successfully  modeled  rats  were
          randomly  divided  into  model  group,  cryptotanshinone  low-dose  group (50  mg/kg),  cryptotanshinone  high-dose  group (100  mg/kg),
          and  cryptotanshinone  high-dose+AMD3100  group (100  mg/kg  cryptotanshinone+2.5  mg/kg  CXCR4  inhibitor AMD3100),  with  10
          rats in each group. Another 10 rats were injected with normal saline instead of VCD as the control group. Rats in each drug group
          were given intragastrical or (and) intraperitoneal injection of the corresponding drug once a day for 4 weeks. The levels of estradiol
         (E2 ),  luteinizing  hormone (LH)  and  follicle-stimulating  hormone (FSH)  in  serum  and  reactive  oxygen  species (ROS),
          malondialdehyde (MDA),  superoxide  dismutase (SOD)  and  glutathione  peroxidase (GSH-Px)  in  ovarian  tissue  were  detected  in
          each group. The morphology of ovarian tissue was observed. The cell apoptosis of ovarian tissue, as well as the mRNA expressions
          of SDF-1, CXCR4 and the protein expressions of caspase-3, B cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), SDF-
          1,  CXCR4  were  detected.  RESULTS  Compared  with  the  control  group,  the  ovarian  atrophied,  the  number  of  primitive  follicles
          decreased,  the  number  of  atretic  follicles  increased,  and  the  damage  was  obvious  in  the  model  group.  Serum  E2  level,  SOD  and
          GSH-Px  levels  in  ovarian  tissue,  the  mRNA  expressions  of  SDF-1  and  CXCR4,  and  the  protein  expressions  of  Bcl-2,  SDF-1  and
                                                              CXCR4  in  ovarian  tissue  were  all  significantly  decreased  or
              Δ 基金项目 河北省自然科学基金项目(No.H2022423334);武汉
                                                              down-regulated;  the  levels  of  FSH  and  LH  in  serum,  ROS
          市 医 学 科 研 项 目(No. WZ19A09);武 汉 市 中 医 药 科 研 项 目(No.
                                                              and MDA levels in ovarian tissue, the cell apoptosis rate, and
          WZ22A10)
             *第一作者 主治医师,硕士。研究方向:妇科杂病的防治。E-                    the  protein  expressions  of  caspase-3  and  Bax  in  ovarian  tissue
          mail:k26awn@163.com                                 were  increased  or  upregulated  significantly  (P<0.05).
              # 通信作者 主任医师,教授,博士。研究方向:中医妇科、生殖内                 Compared  with  model  group,  the  ovarian  tissue  lesions  of  rats
          分泌。E-mail:mahuirong@126.com                         in  cryptotanshinone  low-dose  and  high-dose  groups  were


          · 2998 ·    China Pharmacy  2024 Vol. 35  No. 24                            中国药房  2024年第35卷第24期
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