补肾安胎冲剂调控VHL/HIF-1α信号通路改善复发性流产小鼠母胎界面血管生成的实验研究
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国家自然科学基金项目(81574017)


Bushen Antai Granule Promotes Maternal-Fetal Interface Angiogenesis in Mice with Recurrent Spontaneous Abortion by Regulating the VHL/HIF-1α Signaling Pathway: An Experimental Study
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    摘要:

    目的 研究补肾安胎冲剂对复发性流产小鼠蜕膜组织中希佩尔-林道抑癌基因(Von Hippel-Lindau, VHL)、缺氧诱导因子-1α(hypoxia inducible factor-1α, HIF-1α)的影响,探讨其降低胚胎丢失率的作用机制。方法 以CBA/J雌鼠与BALB/C雄鼠合笼复制正常妊娠小鼠模型,以CBA/J雌鼠和DBA/2雄鼠合笼复制复发性流产(recurrent spontaneous abortion,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10只。妊娠第1天,正常组与模型组采取蒸馏水灌胃,黄体酮组以26 mg/(kg·d)灌胃,补肾安胎冲剂高、中、低剂量组分别按35.1、11.7、3.9 g/(kg·d)灌胃。连续干预15 d后处死小鼠,收集样本,采用ELISA检测各组小鼠血清VHL、HIF-1α水平,采用荧光定量PCR、免疫组织化学法、Western blot法分别检测各组小鼠蜕膜组织中VHL、HIF-1α mRNA及其蛋白表达水平。结果 补肾安胎冲剂显著降低RSA小鼠胚胎丢失率(P<0.05),降低血清和蜕膜组织中VHL水平和VHL mRNA表达水平(P<0.05),升高血清和蜕膜组织中HIF-1α水平和HIF-1α mRNA表达水平(P<0.05),呈现明显的剂量依赖性(P<0.05)。结论 补肾安胎冲剂降低RSA小鼠流产率的机制可能与激活VHL/HIF-1α信号通路有关。

    Abstract:

    Objective To investigate the effect of Bushen Antai Granule on VHL and HIF-1α in the decidual tissue of mice with recurrent spontaneous abortion (RSA) and its mechanism of action in reducing embryo loss rate. Methods Female CBA/J mice and male BALB/C mice were caged to establish a mouse model of normal pregnancy, and female CBA/J mice and male DBA/2 mice were caged to establish a mouse model of RSA. The mice were randomly divided into model group, progesterone group, and high-, middle-, and low-dose Bushen Antai Granule groups, with 10 mice in each group. On day 1 of pregnancy, the mice in the normal group and the model group were given distilled water by gavage, those in the progesterone group were given progesterone at a dose of 26 mg/(kg·d) by gavage,and those in the high-,middle-, and low-dose Bushen Antai Granule groups were given Bushen Antai Granule at a dose of 35.1, 11.7, and 3.9 g/(kg·d), respectively, by gavage. After 15 days of consecutive intervention, the mice were sacrificed and the samples were collected. ELISA was used to measure the serum levels of VHL and HIF-1α, and quantitative real-time PCR, immunohistochemistry, and Western blot were used to measure the mRNA and protein expression of VHL and HIF-1α in decidual tissue. Results Bushen Antai Granule significantly reduced the embryo loss rate of RSA mice (P<0.05), the serum level of VHL, and the mRNA expression of VHL in decidual tissue (P<0.05) and significantly increased the serum level of HIF-1α and the mRNA expression of HIF-1α in decidual tissue (P<0.05), in a dose-dependent manner (P<0.05). Conclusion Bushen Antai Granule can reduce the abortion rate of RSA mice, possibly by activating the VHL/HIF-1α signaling pathway.

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郝乐乐,李伟莉,吴 花,金 雅,王媛中,余欣慧.补肾安胎冲剂调控VHL/HIF-1α信号通路改善复发性流产小鼠母胎界面血管生成的实验研究[J].安徽中医药大学学报,2020,39(1):65-69

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  • 在线发布日期: 2020-01-17