寿胎丸调控HO-1/PGC-1α通路改善线粒体融合-分裂平衡干预复发性流产OA
Shoutai Pills Interventing Recurrent Abortion by Improving Mitochondrial Fusion-Division Balance via Regulating HO-1/PGC-1α Pathway
目的:观察寿胎丸对复发性流产(recurrent spontaneous abortion,RSA)模型小鼠的妊娠保护作用,并基于血红素加氧酶-1(HO-1)/过氧化物增殖体激活受体 γ 共激活因子-1α(PGC-1α)通路及线粒体融合-分裂平衡探讨其作用机制.方法:采用 CBA/J 雌鼠与 DBA/2 雄鼠建立 RSA 小鼠模型,CBA/J 雌鼠与 BALB/c 雄鼠建立正常妊娠小鼠模型.正常妊娠小鼠为正常对照组,RSA 模型小鼠随机分为模型对照组、地屈孕酮 4.6 mg/kg 组、寿胎丸3、6、12 g/kg 组,连续给药12 d.观察并计算小鼠胚胎丢失率;HE 染色观察小鼠蜕膜组织病理改变;透射电镜观察小鼠蜕膜组织中线粒体超微结构变化;流式细胞术及比色法分别检测小鼠蜕膜组织中活性氧(ROS)水平及超氧化物歧化酶(SOD)活力;Western blot 及 RT-PCR 法分别检测小鼠蜕膜组织 MFN1、MFN2、OPA1、DRP1、FIS1、HO-1、PGC-1α 蛋白及 mRNA 表达.结果:与正常对照组相比,模型对照组小鼠胚胎丢失率显著升高(P<0.01),蜕膜组织形态及线粒体超微结构受损,蜕膜组织 ROS 水平显著升高(P<0.01),SOD 活力显著降低(P<0.01),MFN1、MFN2、OPA1、HO-1、PGC-1α 蛋白及 mRNA 表达明显下调(P<0.05 或 P<0.01),蜕膜组织 DRP1、FIS1 蛋白表达及 mRNA 表达显著上调(P<0.01);与模型对照组相比,寿胎丸各剂量组胚胎丢失率明显降低(P<0.05 或 P<0.01),蜕膜组织形态及线粒体超微结构显著改善,ROS 水平显著降低(P<0.01),SOD 活力显著升高(P<0.01),蜕膜组织 MFN1、MFN2、OPA1、HO-1、PGC-1α 蛋白表达及 mRNA 表达明显上调(P<0.05 或 P<0.01),DRP1、FIS1 蛋白表达及 mRNA 表达明显下调(P<0.05 或 P<0.01).结论:寿胎丸可能通过 HO-1/PGC-1α 通路调控线粒体融合-分裂平衡,发挥对复发性流产模型小鼠的妊娠保护作用.
Objective:To observe the pregnancy-protective effect of Shoutai Pills(寿胎丸)on recurrent spontane-ous abortion(RSA)model mice,and to explore its mechanism based on the heme oxygenase-1(HO-1)/peroxisome pro-liferator-activated receptor γ co-activator 1α(PGC-1α)pathway and mitochondrial fusion-division balance.Methods:CBA/J females×DBA/2 males were used to establish RSA mouse models,and CBA/J females×BALB/c males were used to establish normal pregnancy mouse models.Normal pregnant mice were in the normal control group,and RSA model mice were randomly divided into a model control group,a dydrogesterone group(4.6 mg/kg),and Shoutai Pill groups(3,6,and 12 g/kg).After continuous administration for 12 days,the embryo loss rate was calculated and the following aspects were determined in the decidual tissues of each group:pathological changes by hematoxylin and eosin(HE)stai-ning,the ultrastructural changes of mitochondria by transmission electron microscopy,reactive oxygen species(ROS)lev-el by flow cytometry,superoxide dismutase(SOD)level by colorimetric assay,as well as the protein and mRNA expres-sion levels of metabolizable feces nitrogen(MFN1 and MFN2),optic atrophy protein 1(OPA1),dynamin-related protein 1(DRP1),mitochondrial fission protein 1(FIS1),HO-1,and PGC-1α by Western blot and RT-qPCR,respectively.Results:Compared with the normal control group,the embryo loss rate was increased in the model group(P<0.01),the morphology and mitochondrial ultrastructure of decidual tissues were damaged,the ROS level was increased in decidual tissues(P<0.01),the SOD level was decreased(P<0.01),the protein and mRNA expression of MFN1,MFN2,OPA1,HO-1 and PGC-1α were decreased(P<0.05 or P<0.01),and the protein and mRNA expression of DRP1 and FIS1 were increased(P<0.01).Compared with the model control group,the embryo loss rate was reduced in the Shoutai Pill groups(P<0.05 or P<0.01),the morphology and mitochondrial ultrastructure of decidual tissues were improved,the ROS level was decreased(P<0.01),the SOD level was increased(P<0.01),the protein and mRNA expressions of MFN1,MFN2,OPA1,HO-1 and PGC-1α were up regulated(P<0.05 or P<0.01),and the protein and mRNA expres-sions of DRP1 and FIS1 were down regulated(P<0.05 or P<0.01).Conclusion:Shoutai Pills may play a pregnancy protective role in the RSA model mice by regulating mitochondrial fusion-division balance via the HO-1/PGC-1α path-way.
王艳辉;冯玮;史力卉;雷磊
湖南中医药大学中西医结合学院,长沙 410208湖南中医药大学中西医结合学院,长沙 410208湖南中医药大学中西医结合学院,长沙 410208湖南中医药大学中西医结合学院,长沙 410208
复发性流产寿胎丸线粒体融合-分裂平衡血红素加氧酶-1/过氧化物增殖体激活受体γ共激活因子-1α通路
Recurrent spontaneous abortionShoutai PillsMitochondrial fusion-division balanceHO-1/PGC-1α path-way
《中药药理与临床》 2026 (6)
25-31,7
湖南省教育厅重点项目(编号:23A0306)湖南省卫生健康委年度科研项目(编号:C202305016294).
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