Abstract The levels of inflammatory factors in pregnancy-induced hypertension (PIH) are closely correlated with the severity of the disease. The enhanced endoplasmic reticulum (ER) stress response and upregulated iNOS might contribute to the pathophysiology of preeclampsia. Honokiol has been shown to be a potential anti-inflammatory and anti-ER stress agent. However, the effect of honokiol on the inflammation and ER stress has not been investigated in a gestational hypertensive model. The present study aimed to elucidate the role of honokiol in inflammation, ER stress and endothelial/inducible nitric oxide synthase (eNOS/iNOS) in a PIH rat model. Rats with hypoxia-induced PIH were administered honokiol (0, 200, 600, 2000 μg/kg) daily for one week to different groups by intragastric administration. Systolic blood pressure (SBP) and urinary protein concentration were measured via the tail-cuff method and CBB kit. Proinflammatory cytokines and ER-stress markers, VEGF, NO, iNOS and eNOS in the plasma or placental tissue were analyzed by enzyme-linked immunosorbent assay (ELISA), quantitative real time polymerase chain reaction (RT-qPCR), NO assay kit or western blot. The blood pressure and urinary protein level in PIH rats were significantly decreased after honokiol. Honokiol significantly inhibited the elevated levels of proinflammatory cytokines and ER-stress markers, which were accompanied by the upregulation of eNOS, NO and VEGF mRNA in PIH rats. However, the level of iNOS was reduced by honokiol. Our study suggests a beneficial potential of honokiol in PIH rats through inhibition of proinflammatory cytokines and ER stress. Honokiol could be an intriguing therapeutic approach in ER stress related PIH.

中文翻译：

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和厚朴酚抑制妊娠高血压大鼠模型的炎症和内质网应激

摘要 妊娠高血压综合征（PIH）中炎症因子的水平与疾病的严重程度密切相关。增强的内质网 (ER) 应激反应和上调的 iNOS 可能有助于先兆子痫的病理生理学。和厚朴酚已被证明是一种潜在的抗炎和抗 ER 应激剂。然而，尚未在妊娠高血压模型中研究和厚朴酚对炎症和内质网应激的影响。本研究旨在阐明和厚朴酚在 PIH 大鼠模型中的炎症、内质网应激和内皮/诱导型一氧化氮合酶 (eNOS/iNOS) 中的作用。对缺氧诱发的 PIH 大鼠每天给予和厚朴酚 (0, 200, 600, 2000 μg/kg) 1 周，不同组别胃内给药。通过尾套法和 CBB 试剂盒测量收缩压 (SBP) 和尿蛋白浓度。通过酶联免疫吸附测定 (ELISA)、实时定量聚合酶链反应 (RT-qPCR)、NO 测定试剂盒或蛋白质免疫分析法分析血浆或胎盘组织中的促炎细胞因子和 ER 应激标志物、VEGF、NO、iNOS 和 eNOS。污点。和厚朴酚治疗后PIH大鼠的血压和尿蛋白水平显着降低。和厚朴酚显着抑制促炎细胞因子和内质网应激标志物的升高，并伴随着 PIH 大鼠 eNOS、NO 和 VEGF mRNA 的上调。然而，和厚朴酚降低了 iNOS 的水平。我们的研究表明和厚朴酚通过抑制促炎细胞因子和内质网应激对 PIH 大鼠具有有益的潜力。