基于自噬和凋亡探究补肾活血方改善不明原因复发性流产妊娠结局的机制研究  

Mechanism Study of Bushen Huoxue Decoction in Improving Pregnancy Outcomes of Unex⁃plained Recurrent Spontaneous Abortion Based on Autophagy and Apoptosis

作　　者：任佳杰 高倩倩 牛丁忍 郭鲁秦 冯晓玲[2] REN Jia-jie;GAO Qian-qian;NIU Ding-ren;GUO Lu-qin;FENG Xiao-ling(Heilongjiang University of Chinese Medicine,Harbin 150040,China;First Affiliated Hospital,Heilongjiang University of Chinese Medicine,Harbin 150040,China)

机构地区：[1]黑龙江中医药大学研究生院,黑龙江哈尔滨150040 [2]黑龙江中医药大学附属第一医院,黑龙江哈尔滨150040

出　　处：《时珍国医国药》2025年第4期622-627,共6页Lishizhen Medicine and Materia Medica Research

基　　金：国家自然科学基金面上项目(82174421);黑龙江省自然科学基金项目(ZD2021H006);黑龙江省重点研发计划项目(2022ZX60C19);黑龙江中医药大学研究生创新科研项目(2022yjscx003)。

摘　　要：目的依据动物实验从自噬和凋亡角度阐明补肾活血方对不明原因复发性流产的干预机制。方法CBA/J雌鼠与BALB/c雄鼠合笼建立正常妊娠模型,分为空白组和3-甲基腺嘌呤(3-MA)组;与DBA/2雄鼠合笼建立URSA妊娠模型分为模型组和补肾活血方(中药)组,均于发现阴道栓第1日连续给药8d。于雌鼠妊娠第8天灌胃或腹腔注射后2h处死小鼠,并观察每组胚胎吸收情况,计算胚胎吸收率。苏木精-伊红(HE)染色法观察胎盘组织形态学变化。Western-blot检测各组孕鼠胎盘组织中LC3、Beclin1、P62、Caspase3、bax、bcl-2表达水平。结果与空白组相比,模型组和3-MA组孕鼠胚胎吸收率明显增加(P<0.05);与模型组相比,中药组孕鼠胚胎吸收率明显降低(P<0.05)。HE结果显示:中药组胎盘组织中细胞坏死范围减少。Western-blot结果显示:与空白组相比,模型组和3-MA组孕鼠胎盘组织中LC3、Beclin1和bcl-2蛋白表达明显降低,P62、Caspase3和bax、蛋白表达明显升高(P<0.05)。与模型组相比,中药组孕鼠胎盘组织中LC3、Be⁃clin1和bcl-2蛋白表达明显增加,P62、Caspase3和bax蛋白表达明显降低(P<0.05)。结论URSA孕鼠自噬水平降低,细胞凋亡增加,胚胎吸收率高。自噬水平减低可能导致细胞凋亡增加,使胚胎吸收率增加。补肾活血方改善URSA妊娠结局可能与其提高胎盘组织细胞自噬水平、降低细胞凋亡有关。Objective To investigate the intervention mechanism of Bushen Huoxue Decoction(BSHXD)on unexplained recurrent spontaneous abortion(URSA)from the perspective of autophagy and apoptosis based on animal experiments.Methods CBA/J female mice were caged with BALB/c male mice to establish a normal pregnancy model,which were then divided into the blank group and the 3-methyladenine(3-MA)group.DBA/2 male mice were caged with CBA/J females to establish the URSA pregnancy model,which were then divided into the model group and the BSHXD group,and the mice all groups were given drug for 8 consecutive days from the 1st day of the discovery of vaginal plugs.The mice were euthanized 2 hours after gavage or intraperitoneal injection on the 8th day of the female mice’s gestation,embryo resorption was observed in each group,and the embryo resorption rate was calculated.Hematoxylin-e⁃osin(HE)staining was used to observe the histological changes of placenta and Western blot(WB)to detect the expression levels of LC3,Beclin1,P62,Caspase3,bax,and bcl-2 in the placental tissues of pregnant rats in each group.Results Compared with the blank group,the embryo absorption rate in the model group and the 3-MA group was significantly increased(P<0.05);compared with the model group,the embryo absorption rate in the BSHXD group was significantly decreased(P<0.05).HE staining results showed that the extent of cell necrosis in the placental tissues was reduced in the BSHXD group.WB results showed that compared with the blank group,the expression levels of LC3,Beclin1,and Bcl-2 proteins in the placental tissues of the model group and 3-MA group were sig⁃nificantly decreased,while the expression levels of P62,Caspase3,and Bax were significantly increased(P<0.05).Compared with the model group,the expression levels of LC3,Beclin1,and Bcl-2 proteins in the placental tissues of the BSHXD group were significantly increased,while the expression levels of P62,Caspase3,and Bax proteins were significantly decreased(P<0.05).Conclusion URSA pregnant mice

关 键 词：不明原因复发性流产 补肾活血方 细胞自噬 细胞凋亡 

分 类 号：R285.5[医药卫生—中药学]