Department of Obstetrics, Maternity and Child Care Center of Dezhou, Dezhou City, Shandong, 253000, China.
Department of Gynaecology, Maternity and Child Care Center of Dezhou, Dezhou City, Shandong, 253000, China.
Biomed Pharmacother. 2020 Nov;131:110681. doi: 10.1016/j.biopha.2020.110681. Epub 2020 Aug 26.
Gestational diabetes (GDM) is common in pregnancies due to the inflammation and oxidative stress-mediated insulin resistance. In the present study, GDM was induced in the Wistar rats by administering the streptozotocin to elucidate whether the administration of syringin (50 mg/kg/day) during pregnancy could improve maternal glycemia and protect against the complications of GDM. The animals were assessed for their morphological changes in the β-islets of Langerhans and their insulin-producing ability, inflammatory cytokine markers, and the involvement of TLR4/MyD88/NF-κB signaling pathway using RT-PCR. The results demonstrated that the onset of GDM demonstrated pancreatic tissue degeneration in the islets of Langerhans with a significant increase in oxidative stress and reduced antioxidant enzymes. Besides, the mRNA expression levels of TLR4, MyD88, NF-Kβ p65; NLRP3 mRNA were profoundly increased in GDM rats compared to normal pregnant rats. On the other hand, syringin administered GDM rats abrogated the oxidative stress and attenuated the level of the inflammatory cytokines. Intriguingly, the decrease in TLR4 expression and the downstream molecules of MyD88, NF-κB, and NLRP3 were also observed in syringin administered GDM rats that indicate the insulin secretion stimulatory actions of syringin through the suppression of TLR4 signaling. These novel findings of the study provide evidence that syringin could be a probable candidate to be used in the treatment of gestational diabetes in the future.
妊娠期糖尿病(GDM)是由于炎症和氧化应激介导的胰岛素抵抗而在妊娠中常见的疾病。在本研究中,通过给予链脲佐菌素诱导 Wistar 大鼠 GDM,以阐明在妊娠期间给予丁香苷(50mg/kg/天)是否可以改善母体血糖并预防 GDM 的并发症。通过 RT-PCR 评估动物的胰岛β细胞的形态变化及其胰岛素产生能力、炎症细胞因子标志物以及 TLR4/MyD88/NF-κB 信号通路的参与情况。结果表明,GDM 的发生导致胰岛β细胞中的胰腺组织退化,氧化应激显著增加,抗氧化酶减少。此外,与正常妊娠大鼠相比,GDM 大鼠中 TLR4、MyD88、NF-Kβ p65;NLRP3 mRNA 的 mRNA 表达水平显着增加。另一方面,给予丁香苷的 GDM 大鼠减轻了氧化应激并降低了炎症细胞因子的水平。有趣的是,在给予丁香苷的 GDM 大鼠中也观察到 TLR4 表达的降低以及 MyD88、NF-κB 和 NLRP3 的下游分子的降低,这表明丁香苷通过抑制 TLR4 信号来刺激胰岛素分泌。这项研究的新发现提供了证据,表明丁香苷将来可能成为治疗妊娠期糖尿病的候选药物。