Jian Feng, Zhang Xiao
Obstetrics Department, Zibo Central Hospital, Zibo, Shandong, China.
Immunol Invest. 2025 Jan;54(1):68-82. doi: 10.1080/08820139.2024.2418572. Epub 2024 Nov 4.
Preeclampsia is a serious pregnancy complication that can lead to life-threatening conditions such as seizures, strokes, and even death. A dysregulated inflammatory response in the placenta plays a crucial role in the development of preeclampsia. Cordycepin, known for its anti-inflammatory and antioxidant properties, was the focus of this study, which aimed to investigate its effects on preeclampsia.
A preeclampsia-like rat model was established via tail vein injection of lipopolysaccharides (LPS) at a dose of 1 μg/kg in pregnant rats. These rats were then treated with cordycepin at doses of 5, 25, or 50 mg/kg from embryonic day 6 (E6) today 18 (E18). Systolic blood pressures and urinary protein levels were monitored, and pregnancy outcomes, such as fetal body length and weight, were measured. The expression of target genes or proteins was assessed by qPCR, ELISA, and Western blot.
Our findings revealed that cordycepin significantly reduced systolic blood pressure and proteinuria in preeclampsia-like rats. Additionally, cordycepin improved pregnancy outcomes, as shown by increased fetal body length and weight. The treatment also lowered serum sFlt-1 levels, elevated PIGF levels, decreased placental pro-inflammatory cytokine levels (IL-1β, TNF-α, IL-6, MCP-1, and MIP-2), and raised levels of anti-inflammatory cytokine IL-10 level in preeclampsia-like rats. Furthermore, cordycepin helped restore macrophage population imbalances, increasing M1-type macrophage markers (iNOS, TNF-α, and IL-1β) and reducing M2-type macrophage markers (Arg 1, IL-10, and TGF-β).
This study suggests that cordycepin alleviates LPS-induced preeclampsia by reducing placental inflammation and correcting the M1/M2 macrophage imbalance, offering potential therapeutic benefits for managing preeclampsia.
子痫前期是一种严重的妊娠并发症，可导致癫痫发作、中风甚至死亡等危及生命的情况。胎盘炎症反应失调在子痫前期的发展中起关键作用。虫草素以其抗炎和抗氧化特性而闻名，是本研究的重点，旨在研究其对子痫前期的影响。
通过尾静脉注射剂量为1μg/kg的脂多糖（LPS）建立子痫前期样大鼠模型。然后从胚胎第6天（E6）至第18天（E18），用5、25或50mg/kg剂量的虫草素对这些大鼠进行治疗。监测收缩压和尿蛋白水平，并测量妊娠结局，如胎儿体长和体重。通过qPCR、ELISA和蛋白质印迹法评估靶基因或蛋白质的表达。
我们的研究结果表明，虫草素显著降低了子痫前期样大鼠的收缩压和蛋白尿。此外，虫草素改善了妊娠结局，表现为胎儿体长和体重增加。该治疗还降低了子痫前期样大鼠血清中可溶性血管内皮生长因子受体-1（sFlt-1）水平，升高了胎盘生长因子（PIGF）水平，降低了胎盘促炎细胞因子水平（白细胞介素-1β、肿瘤坏死因子-α、白细胞介素-6、单核细胞趋化蛋白-1和巨噬细胞炎症蛋白-2），并提高了抗炎细胞因子白细胞介素-10水平。此外，虫草素有助于恢复巨噬细胞群体失衡，增加M1型巨噬细胞标志物（诱导型一氧化氮合酶、肿瘤坏死因子-α和白细胞介素-1β），并减少M2型巨噬细胞标志物（精氨酸酶1、白细胞介素-10和转化生长因子-β）。
本研究表明，虫草素通过减轻胎盘炎症和纠正M1/M2巨噬细胞失衡来缓解脂多糖诱导的子痫前期，为子痫前期的治疗提供了潜在的益处。
