Department of Obstestrics of People's Hospital of Xinjiang Uygur Autonomous Region, Xinjiang, China.
Kaohsiung J Med Sci. 2021 Mar;37(3):236-244. doi: 10.1002/kjm2.12313. Epub 2020 Oct 22.
Preeclampsia (PE) is a major cause of perinatal and maternal mortality and morbidity, which affects 2% to 8% of pregnancies in the world. The aberrant maternal inflammation and angiogenic imbalance have been demonstrated to contribute to the pathogenesis of PE. This research aimed to investigate the effect of Astragaloside IV (AsIV) in the treatment of PE and the underlying mechanisms. A rat PE-like model was established by tail vein injection of lipopolysaccharide (LPS) and different doses of AsIV (40 and 80 mg/kg) were treated at the same time. Systolic blood pressure, total urine protein and urine volume were observed. Serum and placenta inflammatory cytokines were measured by ELISA kit. The mRNA and protein expression of relative genes were analyzed by qRT-PCR and Western blotting. In PE-like rats, there were obvious increases in systolic blood pressure, total urine protein and urine volume, which were obviously alleviated by treatment with AsIV. Serum levels of interleukin (IL)-1β, tumor necrosis factor alpha (TNF-α), IL-6 and IL-18, as well as IL-4, IL-10, PIGF, VEGF and sFlt-1, were all reversed by treatment with AsIV. Meanwhile, AsIV treatment improved abnormal pregnancy outcomes, such as low litter size and low fetal weight. In addition, AsIV treatment downregulated the mRNA expression of inflammatory gene IL-1β and IL-6 in PE rats model, and AsIV treatment inhibited the activation of TLR-4, NF-κB, and sFlt-1 in the placenta of PE rats. Our findings indicated the first evidence that AsIV alleviated PE-like signs, and this improvement effect is possibly through inhibition of inflammation response via the TLR4/NF-κB signaling pathway.
子痫前期 (PE) 是围产期和孕产妇发病率和死亡率的主要原因，全球有 2%至 8%的妊娠受到影响。异常的母体炎症和血管生成失衡已被证明有助于 PE 的发病机制。本研究旨在探讨黄芪甲苷 (AsIV) 治疗 PE 的作用及其潜在机制。通过尾静脉注射脂多糖 (LPS) 建立大鼠 PE 样模型，并同时给予不同剂量的 AsIV(40 和 80mg/kg)进行治疗。观察收缩压、总尿蛋白和尿量。通过 ELISA 试剂盒测量血清和胎盘炎症细胞因子。通过 qRT-PCR 和 Western blot 分析相对基因的 mRNA 和蛋白表达。在 PE 样大鼠中，收缩压、总尿蛋白和尿量明显升高，AsIV 治疗明显缓解。AsIV 治疗可逆转血清中白细胞介素 (IL)-1β、肿瘤坏死因子-α (TNF-α)、IL-6 和 IL-18 以及 IL-4、IL-10、PIGF、VEGF 和 sFlt-1 的水平。同时，AsIV 治疗改善了异常的妊娠结局，如低胎仔数和低胎儿体重。此外，AsIV 治疗下调了 PE 大鼠模型中炎症基因 IL-1β 和 IL-6 的 mRNA 表达，AsIV 治疗抑制了 TLR4/NF-κB 信号通路中胎盘 PE 大鼠中 sFlt-1 的激活。我们的研究结果首次表明，AsIV 减轻了 PE 样症状，这种改善作用可能是通过抑制 TLR4/NF-κB 信号通路中的炎症反应。
