中脑星细胞衍生的神经营养因子的缺乏在小鼠中加剧了急性胰腺炎

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Hui Li¹, Murong Ma², Wen Wen¹

¹Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.

The American journal of pathology

|January 18, 2026

概括

中脑星细胞衍生神经营养因子 (MANF) 缺乏会通过增加内质网膜 (ER) 应激和炎症,加剧急性胰腺炎 (AP). MANF在胰腺损伤中起着保护作用,在AP模型中观察到取决于性别的效应.

科学领域:

胃肠病学胃肠病学
分子生物学分子生物学
病理学病理学病理学

背景情况:

急性胰腺炎 (AP) 是一种严重的炎症性胰腺疾病.
遗传因素与环境触发因素一起,有助于AP的发病和严重程度.
细胞内膜网膜 (ER) 压力是AP中关键的致病机制,影响蛋白质平衡 (蛋白质平衡).

研究的目的:

为了研究中大脑神经细胞衍生神经变因子 (MANF) 在AP病变发生中的作用.
为了确定MANF缺乏是否会影响实验诱导的AP的严重程度.
探索在AP期间MANF角色中的潜在的性别依赖差异.

主要方法:

使用Cre/loxP系统生成胰腺特异的Manf淘汰赛 (Manf-KO) 小鼠.
在Manf-KO和使用caerulein或酒精的对照小鼠中诱导AP.
评估胰腺损伤标志物,包括ER压力,亡,炎症,再生和脂酶水平.

主要成果:

在两种AP模型中,MANF缺乏会显著恶化胰腺损伤.
在Manf-KO小鼠中观察到升高的ER压力标志物,亡,炎症和脂酶水平.
氧化应激和巨细胞透的性别依赖差异被注意到,特别是在caerulein模型中.

结论:

曼酸对胰腺抵抗压力诱导的损伤至关重要.
MANF 缺乏症通过损害蛋白质稳定和增加炎症而加剧AP严重程度.
在急性胰腺炎的背景下,MANF可能会影响性别特异性反应.

关键词:

滥用酒精滥用酒精滥用酒精滥用酒精滥用酒精氧化应激是一种氧化应激.胰腺损伤胰腺损伤蛋白质稳定症是一种蛋白质稳定症.不折叠的蛋白质反应反应

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