补肾活血方调控Th17分化偏移治疗不明原因复发性流产的作用机制研究OA
Study on the mechanism of Bushen Huoxue Formula(补肾活血方)in regulating Th17 cell dif-ferentiation bias for the treatment of unexplained recurrent spontaneous abortion
目的 探讨补肾活血方通过调控Th17分化偏移治疗不明原因复发性流产(URSA)的作用机制.方法 以CBA/J雌鼠与BABL/c雄鼠合笼构建正常妊娠小鼠模型,以CBA/J雌鼠与DBA/2雄鼠合笼构建URSA妊娠小鼠模型,正常孕鼠作为空白对照组,将URSA孕鼠随机分为模型组、中药组、西药组,各组均15只.各组孕鼠均于发现阴道栓第1天进行灌胃(对照组、模型组予相同容积生理盐水,中药组予补肾活血方中药水煎剂、西药组予地屈孕酮),连续灌胃14d,最后一天给药2h后处死小鼠并取材,观察各组小鼠胚胎吸收率,实时荧光定量聚合酶链式反应(real-time PCR)、蛋白免疫印迹法(Western blot)分别检测蜕膜组织中RORγt、IL-17、IL-22蛋白与mRNA表达水平,酶联免疫吸附(ELISA)测定各组小鼠血清中IL-17、IL-22水平.结果 与对照组比较,模型组胚胎吸收率显著增加(P<0.05),血清中IL-17水平显著上升(P<0.05),IL-22水平明显升高(P<0.01),蜕膜组织中RORγt、IL-17、IL-22蛋白及mRNA表达显著升高(P<0.01).与模型组比较,中药组可以明显降低胚胎吸收率(P<0.05);明显下调RORγt、IL-17、IL-22蛋白与mRNA水平(P<0.01),中药组与西药组两者无显著统计学差异(P>0.05).结论 URSA孕鼠Th17分化发生偏移,补肾活血方可降低相关转录因子RORγt及炎性因子IL-17、IL-22水平逆转Th17细胞分化偏移,降低胚胎吸收率,改善URSA孕鼠妊娠结局.
Objective To explore the mechanism of Bushen Huoxue Formula(补肾活血方,BSHXF)in treating unexplained recurrent spontaneous abortion(URSA)by regulating the bias of Th17 cell differentiation.Methods Normal pregnancy mouse models were estab-lished by mating CBA/J female mice with BABL/c male mice,while URSA pregnancy mouse models were established by mating CBA/J female mice with DBA/2 male mice.The normal pregnant mice served as the blank control group.The URSA pregnant mice were ran-domly divided into the model group,the BSHXF group,and the Western medicine group,with 15 mice in each group.All pregnant mice were gavaged from the first day of vaginal plug detection for 14 consecutive days(the control group and the model group were given the same volume of saline,the BSHXF group,and the Western medicine group,with 15 mice in each group.Intragastric administration began on the first day a vaginal plug was detected(the control and model groups received the same volume of normal saline,the Chinese medicine group received the aqueous decoction of BSHXF,and the Western medicine group received dydrogesterone)and continued for 14 days.On the last day,the mice were sacrificed and samples were collected 2 hours after administration.The embryo absorption rate of each group was observed.Real-time PCR and Western blot(WB)were used to detect the protein and mRNA expression levels of RORγt,IL-17,and IL-22 in the decidual tissue,and ELISA was used to measure the serum levels of IL-17 and IL-22 in mice from each group.Results Compared with the control group,the model group showed a significant increase in the embryo absorption rate(P<0.05),significantly elevated serum IL-17 levels(P<0.05),significantly increased IL-22 levels(P<0.01),and significantly higher protein and mRNA expression of RORγt,IL-17,and IL-22 in the decidual tissue(P<0.01).Compared with the model group,the BSHXF group could significantly reduced the embryo absorption rate(P<0.05)and significantly downregulated the protein and mRNA levels of RORγt,IL-17,and IL-22(P<0.01).There was no significant statistical difference between the BSHXF group and the West-ern medicine group(P>0.05).Conclusion Th17 cell differentiation is biased in URSA pregnant mice.BSHXF can reduce the levels of the related transcription factor RORγt and inflammatory factors IL-17 and IL-22,reverse the bias of Th17 cell differentiation,decrease the embryo absorption rate,and improve the pregnancy outcome in URSA pregnant mice.
冯晓玲;卞圆圆;杨春燕;牛丁忍;韩昕宇
黑龙江中医药大学附属第一医院,黑龙江 哈尔滨 150040黑龙江中医药大学,黑龙江 哈尔滨 150006黑龙江中医药大学,黑龙江 哈尔滨 150006黑龙江中医药大学,黑龙江 哈尔滨 150006黑龙江中医药大学,黑龙江 哈尔滨 150006
医药卫生
补肾活血方不明原因复发性流产辅助性T细胞17RORγtIL-17IL-22
Bushen Huoxue Formula(补肾活血方)Unexplained recurrent spontaneous abortionTh17RORγtIL-17IL-22
《时珍国医国药》 2026 (10)
1830-1835,6
国家自然科学基金面上项目(82174421)中医药循证能力提升项目(国中医药科技中药便函[2023]24号)黑龙江省重点研发计划项目(2022ZX06C19)黑龙江省自然科学基金重点项目(ZD2021H006)重大疑难疾病中西医临床协作项目-先兆流产(国家中医药管理局综合司)项目(ZDYN-2024-A-068)中医药创新团队及人才支持计划项目--中医药治疗不孕不育传承创新团队(国中医药人教函[2025]96号)(ZYYCXTD-C-202404)国家自然科学基金青年基金(82205163)
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