补肾安胎冲剂调节TGF-β1及其下游PI3K/AKT信号通路改善复发性流产小鼠母胎界面血管生成  

Bushen Antai Granule improves angiogenesis at maternal-fetal interface through regulating TGF-β1/PI3K/AKT signaling pathway in recurrent spontaneous abortion mice

作　　者：李伟莉[1] 郝乐乐 金雅 刘明敏 吴花 余欣慧[1] li Weili;Hao Lele;Jin Ya;Liu Mingmin;Wu Hua;Yu Xinhui(Department of Obstetrics and Cynecology,First Affliated Hospital of Anbui University of Chinese Medicine,Anhui 230000,China;Anhui University of Chinese Medicine,Anhui 230000,China)

机构地区：[1]安徽中医药大学第一附属医院妇产科,安徽230000 [2]安徽中医药大学

出　　处：《北京中医药大学学报》2020年第2期125-132,共8页Journal of Beijing University of Traditional Chinese Medicine

基　　金：国家自然科学基金资助项目(No.81574017)。

摘　　要：目的研究补肾安胎冲剂对复发性流产(RSA)小鼠蜕膜组织中转化生长因子-β1(TGF-β1)、磷脂酰肌醇-3-激酶(PI3K)、丝氨酸/苏氨酸蛋白激酶(AKT)相关蛋白的影响,探讨其降低胚胎流产率的作用机制。方法以CBA/J×Balb/c小鼠合笼建立正常妊娠小鼠模型。以DBA/2×CBA小鼠合笼建立RSA小鼠模型,将其随机分为模型组,黄体酮组,补肾安胎冲剂高、中、低剂量组。每组每日以相应药物灌胃,连续干预15 d后处死小鼠,收集样本,肉眼观察各组孕鼠胚胎丢失情况;HE染色法观察每组小鼠蜕膜组织病理形态学改变;采用酶联免疫吸附(ELISA)法检测各组小鼠血清中雌二醇(E2)、孕酮(P)、TGF-β1、PI3K、AKT的含量;采用免疫组化法及蛋白质印迹(Western blot)法检测各组小鼠蜕膜组织中TGF-β1、PI3K、AKT的蛋白表达。结果与正常组相比,模型组小鼠胚胎丢失率升高(P<0.01),血清中E2、P、TGF-β1、PI3K、AKT的含量均下降(P<0.01),蜕膜组织中TGF-β1、PI3K、AKT蛋白表达均下降(P<0.01)。与模型组相比,经药物干预后的小鼠胚胎丢失率均降低(P<0.01),血清中E2、P、TGF-β1、PI3K、AKT的含量均增加(P<0.01),蜕膜组织中TGF-β1、PI3K、AKT的蛋白表达水平均升高(P<0.01),其中补肾安胎冲剂高剂量组更为显著。结论补肾安胎冲剂能降低RSA小鼠流产率,其机制可能是通过上调TGF-β1/PI3K/AKT信号通路,促进RSA小鼠母胎界面血管生成,从而发挥保胎作用。Objective Objective To study the effect of BushenAntai(BSAT) Granule on Transforming Growth Factor β1(TGF-β1), Phosphatidylinositol-3-kinase(PI3 K)and serine/threonine(AKT)related proteins in decidua of mice with recurrent spontaneous abortion, and to explore its mechanism of reducing the rate of embryo abortion. Methods CBA/J × BALB/c mice were caged to establish normal pregnant mice model. The RSA mice model was established by using DBA/2 × CBA mice, which were randomly divided into model group, progesterone group, BushenAntai(BSAT) high dose group, BushenAntai(BSAT)medium-dose group and BushenAntai(BSAT)low-dose group. Each group was gavaged with the corresponding medicine daily.After 15 days of continuous intervention, mice were executed and samples were collected. in each group, the embryo loss was observed by naked eyes;Pathological changes of decidua were observed by hematoxylin eosinstaining. The contents of E2, P, TGF-β1, PI3 K and Akt in serum of mice in each group were detected by enzyme-linked immunosorbent assay(ELISA). The expression of TGF-β1, PI3 K and Akt in decidua was detected by immunohistochemistry and Western blot. Result Compared with the normal group, in the model group the rate of embryo loss was increased(P<0.01), the contents of E2, P, TGF-β1, PI3 K and Akt in serum were decreased(P<0.01), the expression levels of TGF-β1, PI3 K and Akt in decidua were decreased(P<0.01). Compared with the model group, after drug intervention, the rate of embryo loss was decreased(P<0.01), the contents of E2, P, TGF-β1, PI3 K and Akt in serum were increased(P<0.01), and the expression levels of TGF-β1, PI3 K and Akt in decidua were all increased(P<0.01), all of which were most significant in the BSAT high-dose group. Conclusion BSAT Granule is likely to reduce the rate of embryo loss in mice with recurrent spontaneous abortion. Its mechanism may be that through up-regulating TGF-β1/PI3 K/Akt signaling pathway, it could promote the formation of blood vessels at the maternal fetal interface of mi

关 键 词：补肾安胎冲剂 母胎界面 复发性流产 转化生长因子-Β1 PI3K/AKT信号通路 小鼠 

分 类 号：R285.5[医药卫生—中药学]