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阿魏酸通过调节孕期宫内缺氧新生和幼年大鼠海马中的 jumonji C 结构域蛋白 6 和突触素改善认知障碍。

Ferulic acid improves cognitive impairment by regulating jumonji C domain-containing protein 6 and synaptophysin in the hippocampus in neonatal and juvenile rats with intrauterine hypoxia during pregnancy.

机构信息

Department of Human Anatomy and Histoembryology, School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan, 646000, People's Republic of China.

Affiliated Hospital of Traditional Chinese Medicine, Southwest Medical University, Luzhou, Sichuan, 646000, People's Republic of China.

出版信息

Anat Rec (Hoboken). 2023 Oct;306(10):2636-2645. doi: 10.1002/ar.25203. Epub 2023 Mar 15.

DOI:10.1002/ar.25203
PMID:36922637
Abstract

To investigate the impacts of ferulic acid (FA) on jumonji C domain-containing protein 6 (JMJD6) and synaptophysin in the tissues of the hippocampus in neonatal and juvenile rats with intrauterine hypoxia-induced cognitive impairment. The Sprague-Dawley pregnant rats were randomly divided into three groups: control, hypoxia, and hypoxia + FA. On day 14 of pregnancy, the intrauterine hypoxia model was created by placing pregnant rats in the hypoxic and low-pressure experimental chamber for 2 hr a day for 3 days. In the hypoxia + FA group, pregnant rats were injected intraperitoneally with 4% FA, once a day for 7 days. The hypoxia group was treated with equal amounts of saline. After delivery, JMJD6 and synaptophysin mRNA and proteins in the hippocampus regions were detected by in situ hybridization and western blotting. The Morris water maze was used to evaluate cognitive function. The neonatal and juvenile rats in the hypoxia group had significantly increased expression of JMJD6 and decreased expression of synaptophysin protein and synaptophysin I mRNA in the hippocampus than those in the control group. Meanwhile, hypoxia also clearly prolonged the escape latency and shortened the stay time in the target quadrant. FA decreased the expression of JMJD6 and increased the expression of synaptophysin and improved cognitive function compared with those in the hypoxia group. FA probably ameliorated the cognitive impairment by regulating JMJD6 and synaptophysin in the hippocampus of neonatal and juvenile rats who had intrauterine hypoxia during pregnancy.

摘要

目的

探讨孕期宫内缺氧致认知障碍新生及幼鼠海马组织中 JMJD6 与突触素的变化,以及阿魏酸(FA)的干预作用。

方法

将妊娠 Sprague-Dawley 大鼠随机分为对照组、缺氧组、缺氧+FA 组。宫内缺氧模型制作:妊娠第 14 天,将孕鼠置于低氧低压实验舱中,每日 2 小时,连续 3 天。FA 干预组于孕 14 天开始每日腹腔注射 4% FA 4ml/kg,共 7 天;缺氧组注射等体积生理盐水。各组于仔鼠出生后 14 天及 21 天取海马组织,原位杂交及 Western blot 检测 JMJD6、synaptophysin 蛋白及 mRNA 表达,Morris 水迷宫检测认知功能。

结果

与对照组比较,缺氧组新生及幼鼠海马组织中 JMJD6 蛋白及 mRNA 表达上调,synaptophysin 蛋白及 mRNA 表达下调(P<0.05);Morris 水迷宫测试逃避潜伏期延长,目标象限停留时间缩短(P<0.05)。FA 干预后,与缺氧组比较,新生及幼鼠海马组织中 JMJD6 蛋白及 mRNA 表达下调,synaptophysin 蛋白及 mRNA 表达上调(P<0.05);Morris 水迷宫测试逃避潜伏期缩短,目标象限停留时间延长(P<0.05)。

结论

孕期宫内缺氧可能通过上调 JMJD6 表达、下调 synaptophysin 表达导致新生及幼鼠认知功能障碍,FA 可能通过下调 JMJD6 表达、上调 synaptophysin 表达改善认知功能。

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