Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Hefei, China.
National Health Commission (NHC) Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), Hefei, China.
Front Endocrinol (Lausanne). 2022 Nov 17;13:914030. doi: 10.3389/fendo.2022.914030. eCollection 2022.
High mobility group box protein 1 (HMGB1) is considered as a kind of sterile inflammatory mediators, which is an overexpression in patients with unexplained recurrent spontaneous abortion (URSA). Specific targeting effect of aspirin on HMGB1 has been revealed. Our previous studies have explored the application of HMGB1 as a therapeutic target of aspirin in URSA disease of mice model and human, but the dynamic process of aspirin downregulating HMGB1 concentration has not been demonstrated.
From December 2018 to November 2020, women with URSA ( = 91) and control women ( = 90) with no history of recurrent abortion or adverse pregnancy were included in the Reproductive Medicine Center of the First Affiliated Hospital of Anhui Medical University. ELISA was applied to detect the concentrations of HMGB1 and IFN-γ in the peripheral blood. Thirty-one URSA patients were monitored for low-dose aspirin treatment (2 and 4 weeks), the changes of HMGB1 and IFN-γ concentrations in peripheral blood of URSA patients before and after using aspirin were compared, and pregnancy outcomes after aspirin treatment were followed up.
The levels of HMGB1 in peripheral blood were significantly higher in URSA patients compared with controls, decreasing trends of HMGB1 and IFN-γ concentrations in plasma of URSA patients were observed after treatment with low-dose aspirin continuously, and the expression of HMGB1 was positively correlated with IFN-γ. There were no birth abnormalities in the babies of the URSA patients treated with aspirin.
High levels of HMGB1 may be one of the pathogenesis of URSA. Low-dose aspirin may provide protective effect on the HMGB1-triggered URSA.
高迁移率族蛋白 B1(HMGB1)被认为是一种无菌性炎症介质,在不明原因复发性自然流产(URSA)患者中过度表达。阿司匹林对 HMGB1 的特异性靶向作用已被揭示。我们之前的研究探讨了将 HMGB1 作为阿司匹林治疗 URSA 疾病的靶点在小鼠模型和人类中的应用,但阿司匹林下调 HMGB1 浓度的动态过程尚未得到证实。
本研究纳入了 2018 年 12 月至 2020 年 11 月在安徽医科大学第一附属医院生殖医学中心就诊的 URSA 患者(n=91)和无复发性流产或不良妊娠史的对照组女性(n=90)。采用酶联免疫吸附试验(ELISA)检测外周血中 HMGB1 和 IFN-γ的浓度。对 31 例 URSA 患者进行低剂量阿司匹林治疗(2 和 4 周)监测,比较 URSA 患者使用阿司匹林前后外周血中 HMGB1 和 IFN-γ浓度的变化,并随访阿司匹林治疗后的妊娠结局。
URSA 患者外周血中 HMGB1 水平明显高于对照组,URSA 患者经低剂量阿司匹林连续治疗后,HMGB1 和 IFN-γ 浓度呈下降趋势,HMGB1 的表达与 IFN-γ呈正相关。接受阿司匹林治疗的 URSA 患者的婴儿均无出生异常。
HMGB1 水平升高可能是 URSA 的发病机制之一。低剂量阿司匹林可能对 HMGB1 触发的 URSA 具有保护作用。