南方医科大学学报

南方医科大学学报 ›› 2023, Vol. 43 ›› Issue (2): 265-270.doi: 10.12122/j.issn.1673-4254.2023.02.15

• • 上一篇    下一篇

补肾活血方通过下调JAK2/STAT3通路改善小鼠的复发性流产

赵佳琳，陈 萍，徐广立，孙建华，阮媛媛，薛苗苗，吴悦靓   

  1. 河南中医药大学第一临床医学院，河南 郑州 450000；河南中医药大学第一附属医院妇产科，河南 郑州 450000；河南中医药大学第一附属医院生殖医学科二区，河南 郑州 450000
  • 出版日期:2023-02-20 发布日期:2023-03-16

Bushen Huoxue Fang improves recurrent miscarriage in mice by down-regulating the JAK2/STAT3 pathway

ZHAO Jialin, CHEN Ping, XU Guangli, SUN Jianhua, RUAN Yuanyuan, XUE Miaomiao, WU Yueliang   

  1. First Clinical Medical College, Henan University of Chinese Medicine, Zhengzhou 450000, China; Department of Obstetrics and Gynecology, First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450000, China; Division II of Department of Reproductive Center, The first affiliated hospital of Henan University of Chinese Medicine, Henan Zhengzhou 450000, China
  • Online:2023-02-20 Published:2023-03-16

RichHTML

24

PDF

367

摘要： 目的 基于胎盘组织酪氨酸激酶（JAK2）与转录激活子（STAT3）信号通路，探讨补肾活血法治疗复发性流产（RSA）的疗效。方法 CBA/J雌鼠与BALB/c雄鼠合笼建立正常对照组；CBA/J雌鼠与DBA/2雄鼠合笼建立RSA小鼠模型，按照随机数字表法分为模型组、地屈孕酮组和补肾活血法组，6 只/组，于妊娠第1天起，补肾活血法组予补肾活血方（BSHXF）灌胃，地屈孕酮组予以地屈孕酮溶液，正常对照组及模型组予以等体积蒸馏水，干预12 d。ELISA测定各组小鼠血清抗凝血酶原Ⅲ（AT-Ⅲ）、活化蛋白C（APC）、组织型纤溶酶原激活因子（t-PA）、孕酮（P）、人绒毛膜促性腺激素（HCG）、雌二醇（E2）含量；HE染色法观察小鼠子宫内膜形态变化；Western blot法测定小鼠胎盘p-JAK2、p-Stat3、BCL-2表达。结果 与正常组相比，模型组胚胎丢失率明显升高，血清AT-Ⅲ、t-PA、P、APC水平降低，p-JAK2、p-STAT3、Bax蛋白相对表达量升高，Bcl-2蛋白相对表达量降低（P<0.05）；与正常组比较，模型组AT-Ⅲ、t-PA、P、APC、HCG水平均降低（P<0.05）。与模型组比较，BSHXF组与地屈孕酮组血清AT-Ⅲ、t-PA、HCG水平均升高；BSHXF组APC水平降低，地屈孕酮组血清P水平升高（P<0.05）。结论 补肾活血法可通过下调JAK2/STAT3通路改善血栓前状态，抑制细胞凋亡，有效提高妊娠率。

关键词: JAK2/STAT3；复发性流产；补肾活血方；血栓前状态

Abstract: Objective To investigate the efficacy of Bushen Huoxue Fang (BSHXF, a traditional Chinese medicine formula) for improving recurrent spontaneous abortion (RSA) in mice and the role of tyrosine kinase (JAK2) and transcriptional activator (STAT3) signaling pathway in its therapeutic mechanism. Methods Female CBA/J mice were caged with male DBA/2 mice to establish RSA mouse models, which were randomly divided into model group, dydrogesterone group and BSHXF group, with the female mice caged with male BALB/c mice as the control group (n=6). From the first day of pregnancy, the mice were subjected to daily intragastric administration of BSHXF, dydrogesterone, or distilled water (in control and model groups) for 12 days. After the treatments, serum levels of antithrombin III (AT-III), activated protein C (APC), tissue plasminogen activator (t-PA), progesterone, human chorionic gonadotropin (HCG), and estradiol (E2) were detected in each group using ELISA. HE staining was used to observe the morphological changes of the endometrium of the mice. Western blotting was performed to determine the expressions of p-JAK2, p-Stat3 and Bcl-2 in the placenta of the mice. Results Compared with the control mice, the mouse models of RSA showed a significantly increased embryo loss rate with decreased serum levels of AT- III, T- PA, progesterone, APC and HCG, increased placental expressions of p-JAK2, p-STAT3 and Bax, and decreased expression of Bcl-2 (P<0.05). Treatments with BSHXF and dydrogesterone both increased serum levels of AT-III, t-PA and HCG in the mouse models; Serum APC level was significantly reduced in BSHXF group and serum progesterone level was significantly increased in dydrogesterone group (P<0.05). Conclusion BSHXF can improve the prethrombotic state and inhibit cell apoptosis by downregulating the JAK2/STAT3 pathway to increase the pregnancy rate in mouse models of RSA.

Key words: JAK2/STAT3; recurrent spontaneous abortion; Bushen Huoxue Fang; prethrombotic state