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蝎毒对啮齿动物模型休息和活动期下丘脑-垂体-肾上腺轴的免疫毒性作用。

Immune-toxicity effects of scorpion venom on the hypothalamic pituitary adrenal axis during rest and activity phases in a rodent model.

机构信息

USTHB, Faculty of Biological Sciences, Laboratory Cellular and Molecular Biology, Department Cellular and Molecular Biology, BP32, EL Alia, Bab Ezzouar 16111, Algiers, Algeria.

USTHB, Faculty of Biological Sciences, Laboratory Cellular and Molecular Biology, Department Cellular and Molecular Biology, BP32, EL Alia, Bab Ezzouar 16111, Algiers, Algeria.

出版信息

Comp Biochem Physiol C Toxicol Pharmacol. 2020 Sep;235:108787. doi: 10.1016/j.cbpc.2020.108787. Epub 2020 May 4.

DOI:10.1016/j.cbpc.2020.108787
PMID:32380264
Abstract

Scorpion venom is a complex mixture of peptides and proteins, rich in toxins. Its toxicological effects are related to central disruptions and autonomic disturbances, organ failure, as well as an excessive systemic inflammatory response. Since the role of the hypothalamic pituitary adrenal (HPA) axis is central in the neuroendocrine-immunological axis, the purpose of this study was, therefore, to examine the immunotoxic effect of Androctonus australis hector (Aah) venom on HPA-axis in synchronised-mice model. Taking into account the circadian activity of the HPA-axis, the variations of adrenocorticotropic hormone and corticosterone plasma levels, oxidative stress as well as inflammatory markers in cerebral, hypothalamic and adrenal tissue homogenates were investigated during the rest and activity phases of animals. Histopathology study was also performed. Results showed that Aah venom activated the HPA axis. This response seems to be dependent on time of envenomation, as a higher hormone levels were more operative during the active phase than in the rest phase when compared to time-matched control. The local toxicity-effects following Aah envenomation revealed an imbalance in oxidative stress with a higher antioxidant defences in darkness hypothalamic and cerebral tissues. Furthermore, there were significantly higher levels in vascular permeability in hypothalamic and cerebral tissues accompanied by a concomitant increase in immune-cell infiltration and/or activation as shown by expression of CD68 and myeloperoxidase activity during the active phase compared with the rest phase. Overall results suggested that Aah venom had a toxic impact on different HPA-axis areas and the effect varies according to the time of envenomation.

摘要

蝎毒是一种复杂的肽和蛋白质混合物,富含毒素。其毒性作用与中枢神经系统紊乱和自主神经紊乱、器官衰竭以及过度的全身炎症反应有关。由于下丘脑-垂体-肾上腺 (HPA) 轴在神经内分泌-免疫轴中的作用至关重要,因此本研究旨在检查安德罗克托斯 australis hector (Aah) 毒液对同步化小鼠模型 HPA 轴的免疫毒性作用。考虑到 HPA 轴的昼夜活动,研究了在动物的休息和活动阶段,促肾上腺皮质激素和皮质酮血浆水平、氧化应激以及大脑、下丘脑和肾上腺组织匀浆中的炎症标志物的变化。还进行了组织病理学研究。结果表明,Aah 毒液激活了 HPA 轴。这种反应似乎取决于毒液的时间,与时间匹配的对照组相比,在活动期激素水平更高。Aah 中毒后的局部毒性作用显示氧化应激失衡,黑暗时下丘脑和大脑组织的抗氧化防御能力更高。此外,与休息期相比,在活动期下丘脑和大脑组织的血管通透性显著升高,同时免疫细胞浸润和/或激活增加,如 CD68 表达和髓过氧化物酶活性所示。总体结果表明,Aah 毒液对不同的 HPA 轴区域具有毒性影响,并且这种影响根据毒液的时间而变化。

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