| Objective To explore the mechanism of Heshi Bushen Yiqi Huoxue Decoction on regulating status of maternal-fetal interface in RSA mice suffering ACA positive prethrombus status based on JAK ∕ STAT3 signaling pathway. Methods
Establishing RSA mice model suffering ACA positive prethrombus with humanβ2-GPⅠ as derivant. Fifty completed the modeling process mice were divided into five groups . Specifically refers to blank control group (treated with normal saline), model control group (treated with β2-GPⅠ), positive control group (treated with aspirin), and Heshi Bushen Yiqi Huoxue decoction of low and high dose groups.
Pregnancy mice received intragastric administration of the different test compound daily for two weeks form the first day of conception observed. Mice were euthanized at 15th day of their pregnancy to calculate the embryo resorption rate, and the blood and tissue samples were collected to analyse the ACA levels in peripheral blood by means of ELISA. The expression of JAK, GP130, p-STAT3, and PCNA in placental and decidual tissues was analyzed by immunohistochemistry, whereas STAT3 and p-STAT3 protein levels were evaluated by Western blot analysis. Results Compared with the model group, the aspirin control, low-dose Chinese medicine, and high-dose Chinese medicine groups demonstrated: Significantly lower embryo loss rates [(24.49±11.17)%, (16.18±11.92)%, and (15.94±8.01)% vs. (42.53±15.12)%, respectively; P<0.05]; Markedly reduced serum ACA titers [(93.16±6.75) pg/mL, (92.31±5.22) pg/mL, and (81.60±5.18) pg/mL vs. (419.51±94.00) pg/mL; P<0.05]; and
Significantly increased protein expression at the maternal-fetal interface: placental JAK [(1.44±0.53), (1.43±0.50), (1.51±0.35) vs. (0.21±0.31); P<0.05], placental p-STAT3 [(1.83±0.41), (2.00±0.63), (2.00±0.71) vs. (0.20±0.45); P<0.05], decidual p-STAT3 [(2.50±0.55), (2.67±0.52), (2.80±0.84) vs. (1.39±0.99); P<0.05], placental PCNA [(2.88±0.36), (3.00±0.58), (2.91±0.68) vs. (3.50±0.59); P<0.05], decidual PCNA [(1.07±0.09), (1.09±0.07), (1.09±0.09) vs. (0.79±0.06); P<0.05].
Conclusion Heshi Bushen Yiqi Huoxue Decoction can reduce ACA titers, activate the JAK-STAT3 signaling pathway, and promote cell proliferation. These effects improve the embryo implantation environment and pregnancy outcomes in ACA-positive mice, providing experimental evidence for clinical prevention and treatment. |