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没食子儿茶素没食子酸酯(EGCG)通过 eNOS/Nrf2/HO-1 通路减轻子痫前期(PE)样大鼠的炎症和内皮功能障碍,改善妊娠结局。

Epigallocatechin gallate (EGCG) alleviates inflammation and endothelial dysfunction and improves pregnancy outcomes in preeclampsia (PE)-like rats via eNOS/Nrf2/HO-1 pathway.

机构信息

Tianjin Central Hospital of Obstetrics and Gynecology, Tianjin Key Laboratory of Human Development and Reproductive Regulation, Tianjin 300100, China.

Tianjin Central Hospital of Obstetrics and Gynecology, Tianjin Key Laboratory of Human Development and Reproductive Regulation, Tianjin 300100, China.

出版信息

J Reprod Immunol. 2024 Aug;164:104263. doi: 10.1016/j.jri.2024.104263. Epub 2024 May 22.

DOI:10.1016/j.jri.2024.104263
PMID:38838579
Abstract

BACKGROUND AND PURPOSE

Epigallocatechin gallate (EGCG), a natural antioxidant, has shown protective effect in many diseases. We explore the effect and potential regulatory mechanisms of EGCG in preeclampsia (PE)-like rats.

METHODS AND MATERIALS

PE was mimicked in pregnant rats. EGCG was orally administered at a dosage of 25(Low, L) or 50 mg/kg (High, H) from gestational day (GD) 6-17. The blood pressure signatures, heart rates were monitored. The 24-h proteinuria and serum were analyzed. On GD 18, rats were sacrificed, and pups and placentas were weighed. Kidneys and placentas were analyzed using immunohistochemistry (IHC) and hematoxylin-eosin staining (H&E). Placentas were examined using western blot for sFlt1, eNOS, Nrf2, HO-1, SLC7A11. MDA, GSH, GPx and Fe2+ were measured.

RESULTS

EGCG inhibits systolic blood pressure, BUN, CREA, ALT, AST, UA and proteinuria levels in PE-like rats. EGCG enhances the pup weight and crown-rump length and reduces the rate of fetus growth restriction in PE group. Endothelial dysfunction and infiltration of inflammatory cells were found in kidney cortex and placenta tissues in PE group and were inhibited by EGCG treatment. sFlt1 was activated in placentas in PE group and inhibited by EGCG while eNOS/Nrf2/HO-1 were inhibited in PE group and restored by EGCG. MDA and Fe concentrations were elevated in PE group and reduced by EGCG while the GSH level, SLC7A11 and the GPx activity were inhibited in PE group and restored by EGCG.

CONCLUSION

EGCG alleviates inflammation, endothelial dysfunction and placental ferroptosis, improves pregnancy outcomes in PE-like rats via eNOS/Nrf2/HO-1.

摘要

背景与目的

表没食子儿茶素没食子酸酯(EGCG)是一种天然抗氧化剂,在许多疾病中显示出保护作用。我们探索 EGCG 在子痫前期(PE)样大鼠中的作用及潜在调节机制。

方法与材料

通过给怀孕大鼠注射药物来模拟 PE。EGCG 以 25(低,L)或 50mg/kg(高,H)的剂量从妊娠第 6-17 天经口给药。监测血压特征和心率。分析 24 小时蛋白尿和血清。在妊娠第 18 天,大鼠被处死,测量幼仔和胎盘的重量。使用免疫组织化学(IHC)和苏木精-伊红染色(H&E)分析肾脏和胎盘。使用 Western blot 分析胎盘中的可溶性 fms 样酪氨酸激酶 1(sFlt1)、内皮型一氧化氮合酶(eNOS)、核因子红细胞 2 相关因子 2(Nrf2)、血红素加氧酶 1(HO-1)、溶质载体家族 7 成员 11(SLC7A11)。测量丙二醛(MDA)、谷胱甘肽(GSH)、谷胱甘肽过氧化物酶(GPx)和二价铁(Fe2+)。

结果

EGCG 抑制 PE 样大鼠的收缩压、BUN、CREA、ALT、AST、UA 和蛋白尿水平。EGCG 增加幼仔体重和头臀长,并降低 PE 组胎儿生长受限的发生率。在 PE 组的肾脏皮质和胎盘组织中发现内皮功能障碍和炎症细胞浸润,EGCG 治疗抑制了这些变化。sFlt1 在 PE 组的胎盘组织中被激活,而 EGCG 抑制了它,eNOS/Nrf2/HO-1 在 PE 组中受到抑制,而 EGCG 恢复了它们。MDA 和 Fe 浓度在 PE 组中升高,而 EGCG 降低了它们,而 GSH 水平、SLC7A11 和 GPx 活性在 PE 组中受到抑制,而 EGCG 恢复了它们。

结论

EGCG 通过 eNOS/Nrf2/HO-1 减轻炎症、内皮功能障碍和胎盘铁死亡,改善 PE 样大鼠的妊娠结局。

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