血栓调节蛋白可改善热应激小鼠的认知缺陷

IF 4.5 2区 医学 Q1 CLINICAL NEUROLOGY
Cheng-Hsien Lin, Ling-Yu Tang, Lin-Yu Wang, Ching-Ping Chang
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引用次数: 0

摘要

背景:血栓调节蛋白(TM)具有抗凝和抗炎作用,可提高脓毒性休克患者的存活率。中暑在很多方面与脓毒性休克相似。我们测试了 TM 是否能改善热应激小鼠的认知缺陷和相关致病因素:方法:成年雄性小鼠暴露于热休克(33 摄氏度,每天 2 小时,连续 7 天),诱发认知障碍。第一次热应激试验后立即注射重组人可溶性血栓调节蛋白(TM,1 毫克/千克,静脉注射),然后连续 7 天每天注射一次。我们进行了Y-迷宫、新目标识别和被动回避测试来评估认知功能。对血浆中的脂多糖、高迁移率基团框 1 (HMGB1)、凝血参数以及血浆和组织中的炎症和氧化应激标记物水平进行了生化测定。对十二指肠和海马切片进行了免疫组化染色。结果表明:与对照组相比,HS小鼠的肠道和血脑屏障通透性均有所下降:结果:与对照组相比,接受 TM 治疗的 HS 小鼠认知障碍程度较轻,应激反应、肠道屏障破坏、内毒素血症、血脑屏障破坏以及心脏、十二指肠和海马组织的炎症、氧化和凝血损伤程度较轻,血浆 HMGB1 增高。除了减少认知障碍外,TM疗法还能缓解热应激小鼠的上述所有并发症:研究结果表明,热应激可导致应激反应加剧、内毒素血症、肠道屏障破坏、血脑屏障破坏、海马体炎症、凝血病和氧化应激,这些可能是认知障碍的致病因素。血栓调节蛋白是一种抗炎、抗氧化和抗凝血剂,它能抑制热应激引起的小鼠认知障碍。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Thrombomodulin Improves Cognitive Deficits in Heat-Stressed Mice.

Background: Thrombomodulin (TM) exerts anticoagulant and anti-inflammatory effects to improve the survival of patients with septic shock. Heat stroke resembles septic shock in many aspects. We tested whether TM would improve cognitive deficits and related causative factors in heat-stressed (HS) mice.

Methods: Adult male mice were exposed to HS (33°C for 2 hours daily for 7 consecutive days) to induce cognitive deficits. Recombinant human soluble TM (1 mg/kg, i.p.) was administered immediately after the first HS trial and then once daily for 7 consecutive days. We performed the Y-maze, novel objective recognition, and passive avoidance tests to evaluate cognitive function. Plasma levels of lipopolysaccharide (LPS), high-mobility group box 1 (HMGB1), coagulation parameters, and both plasma and tissue levels of inflammatory and oxidative stress markers were biochemically measured. The duodenum and hippocampus sections were immunohistochemically stained. The intestinal and blood-brain barrier permeability were determined.

Results: Compared with controls, HS mice treated with TM had lesser extents of cognitive deficits, exacerbated stress reactions, gut barrier disruption, endotoxemia, blood-brain barrier disruption, and inflammatory, oxidative, and coagulatory injury to heart, duodenum, and hippocampal tissues, and increased plasma HMGB1. In addition to reducing cognitive deficits, TM therapy alleviated all the abovementioned complications in heat-stressed mice.

Conclusions: The findings suggest that HS can lead to exacerbated stress reactions, endotoxemia, gut barrier disruption, blood-brain barrier disruption, hippocampal inflammation, coagulopathy, and oxidative stress, which may act as causative factors for cognitive deficits. TM, an anti-inflammatory, antioxidant, and anti-coagulatory agent, inhibited heat stress-induced cognitive deficits in mice.

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来源期刊
CiteScore
8.40
自引率
2.10%
发文量
230
审稿时长
4-8 weeks
期刊介绍: The central focus of the journal is on research that advances understanding of existing and new neuropsychopharmacological agents including their mode of action and clinical application or provides insights into the biological basis of psychiatric disorders and thereby advances their pharmacological treatment. Such research may derive from the full spectrum of biological and psychological fields of inquiry encompassing classical and novel techniques in neuropsychopharmacology as well as strategies such as neuroimaging, genetics, psychoneuroendocrinology and neuropsychology.
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