Experimental Study on Bushen Huoxue Prescription in the Regulation of Maternal- Fetal Interface Angiogenesis in Mice with Recurrent Spontaneous Abortion
Abstract: Objective: To observe the effect of Bushen Huoxue prescription on vascular endothelial growth factors(VEGF), soluble fms- like tyrosine kinase receptor- 1(sFlt- 1), hypoxia inducible factor- 1α (HIF-1α) and transforming growth factor-β(TGF-β) in mice with recurrent spontaneous abortion(RSA),and to explore its mechanism of reducing abortion rate. Methods: A total of 40 RSA mice models were randomly divided into the model group,the Bushen Huoxue prescription groups of low- dose,mediumdose and high-dose(6.53,13.06,26.13 g/kg),with 10 mice in each group,and 10 normal pregnant mice were involved in the blank group. The Bushen Huoxue prescription groups of low-dose,medium-dose and high- dose were given corresponding doses of Bushen Huoxue prescription granules aqueous solution by gavage,and the blank group and the model group were given equal volume distilled water by gavage. After 14 days of continuous administration, the mice were sacrificed and samples were collected. The loss of embryos and histopathological changes of decidua were observed. The levels of VEGF, sFlt- 1, HIF- 1α and TGF-β in serum were detected by ELISA. The mRNA expressions of VEGF,sFlt-1,HIF-1α and TGF-β in decidua tissue were detected by RT- PCR. Results: Compared with those in the blank group, the embryo loss rate,the levels of HIF-1α and sFlt-1 in serum,and mRNA expressions of HIF-1α and sFlt-1 in decidua tissue of mice in the model group were increased (P<0.05),and the mRNA expressions of VEGF and TGF- β in decidua tissue and levels of VEGF and TGF- β in serum were decreased(P<0.05); the decidua tissue of mice in the model group showed abnormal cell morphology,disordered arrangement and obvious distribution of inflammatory cells. Compared with those in the model group,the embryo loss rate, levels of HIF-1α and sFlt-1 in serum and mRNA expressions of HIF-1α and sFlt-1 in decidua tissue of mice in the Bushen Huoxue prescription groups of medium-dose and high-dose were decreased(P<0.05),and the mRNA expressions of VEGF and TGF-β in decidua tissue and levels of VEGF and TGF-β in serum were increased(P<0.05). Among them,the improvement in the Bushen Huoxue prescription group of high-dose group was more obvious(P<0.05). After the intervention of Bushen Huoxue prescription,the pathological changes of decidua tissues of mice in each administration group were significantly improved. Conclusion: Bushen Huoxue prescription can regulate the expressions of VEGF, TGF- β, sFlt- 1, and HIF- 1α to promote the angiogenesis of maternal fetal interface,reduce the abortion rate of RSA mice,and play a role in fetal protection.