Shao Liang, Wang Nansu, Yan Yan, Tan Yali, Wu Qin, Lei Lei, Wang Mingming, Liu Ling
Department of Emergency, the First Affiliated Hospital of Hunan Traditional Chinese Medicine College, Zhuzhou, Hunan, China.
Department of TCM Gynaecology, the First Affiliated Hospital of Hunan Traditional Chinese Medicine College, Zhuzhou, Hunan, China.
Iran J Basic Med Sci. 2024;27(6):685-694. doi: 10.22038/IJBMS.2024.72049.15662.
Tubal factor infertility (TFI) is common female infertility responsible for a large portion of female factor infertility. This study reveals the effect of the quercetin of Huoxuehuayu Tongluo Decoction with azithromycin on the pregnancy rate and inflammation of TFI female rats.
Female Sprague Dawley rats were constructed into the TFI model and treated with quercetin, Huoxuehuayu Tongluo Decoction, and combination therapy (quercetin and azithromycin). Pregnancy rate and litter size were measured. Network pharmacology was applied to analyze the interaction between Huoxuehuayu Tongluo Decoction and TFI. The combination of quercetin and IL-6 was analyzed by molecular docking. HE staining and electron microscopy were used to observe the histopathology and ultrastructure of fallopian tube tissues. The TNF-α, IL-1β, IL-6, IL-8, and MPO levels were detected by ELISA. The activation of JAK/STAT, MAPK, and NF-κB p65 pathways was detected by western blot or immunohistochemistry.
Quercetin was the main active component of Huoxuehuayu Tongluo Decoction, and could bind to IL-6 in TFI. Target genes were enriched in the IL-17 signaling pathway, JAK-STAT signaling pathway, inflammatory disease, etc. Under the quercetin and azithromycin combination therapy, both rat pregnancy rates and litter sizes increased significantly. quercetin and azithromycin alleviated the symptoms of hydrosalpinx and inflammatory damage in fallopian tube tissues. The phosphorylation of JAK/STAT and MAPK pathways and NF-κB p65 translocation to the nucleus were significantly inhibited by the quercetin and azithromycin therapy.
Quercetin and azithromycin combination therapy inhibited inflammation and phosphorylation of JAK/STAT and MAPK pathways to improve TFI inflammation and pregnancy function.
输卵管因素不孕症(TFI)是导致女性不孕的常见原因,在女性因素不孕症中占很大比例。本研究揭示了活血化淤通络汤中的槲皮素联合阿奇霉素对TFI雌性大鼠妊娠率和炎症的影响。
将雌性Sprague Dawley大鼠构建成TFI模型,并分别用槲皮素、活血化淤通络汤及联合疗法(槲皮素和阿奇霉素)进行治疗。测量妊娠率和产仔数。应用网络药理学分析活血化淤通络汤与TFI之间的相互作用。通过分子对接分析槲皮素与白细胞介素-6(IL-6)的结合情况。采用苏木精-伊红(HE)染色和电子显微镜观察输卵管组织的组织病理学和超微结构。通过酶联免疫吸附测定(ELISA)检测肿瘤坏死因子-α(TNF-α)、IL-1β、IL-6、IL-8和髓过氧化物酶(MPO)水平。通过蛋白质免疫印迹法或免疫组织化学检测Janus激酶/信号转导子和转录激活子(JAK/STAT)、丝裂原活化蛋白激酶(MAPK)和核因子κB p65(NF-κB p65)信号通路的激活情况。
槲皮素是活血化淤通络汤的主要活性成分,且能与TFI中的IL-6结合。靶基因富集于IL-17信号通路、JAK-STAT信号通路、炎症性疾病等。在槲皮素和阿奇霉素联合治疗下,大鼠的妊娠率和产仔数均显著增加。槲皮素和阿奇霉素减轻了输卵管积水症状和输卵管组织的炎症损伤。槲皮素和阿奇霉素治疗显著抑制了JAK/STAT和MAPK信号通路的磷酸化以及NF-κB p65向细胞核的转位。
槲皮素和阿奇霉素联合治疗可抑制炎症以及JAK/STAT和MAPK信号通路的磷酸化,从而改善TFI炎症和妊娠功能。