Supplementary Material for: Zinc Alleviates Lipopolysaccharide Interference with Both Body Temperature and Sickness Behavior in Virgin Female Rats

Objectives: Previous studies from our group showed that lipopolysaccharide (LPS) exposure induces several signs of sickness behavior, including a decrease in food consumption, body weight gain, adipsia, and a biphasic effect in tympanic temperature with a first phase of hypothermia, followed by an increased tympanic temperature. LPS can activate a chain of nonspecific host responses, including the immune response, and decreased zinc levels. In addition, there are differences in the immune response between males and females, particularly fever, with sex hormones interfering with body temperature. This study aims to characterize the effects of zinc treatment on tympanic temperature, body weight gain, food and water consumption, and general activity in open field of virgin female rats exposed to a dose of LPS that was previously reported to induce sickness behavior. Methods: Virgin female Wistar rats were treated with either saline (S) or LPS. One hour later, the S group received another injection of saline (S + S group), half of the LPS group received saline (LPS + S group) and the other half received zinc (LPS + Zn group). Tympanic temperature, body weight, and water and food consumption were measured for 96 h. Measurements and observations started 2 h after LPS administration. Results: Treatment with zinc attenuated LPS-increased temperature, decreased the body weight gain and food consumption, and water consumption was increased. Conclusion: Zinc treatment is beneficial as it reduces the increased tympanic temperature induced by LPS, but it does not influence other sickness behavior caused by exposure to LPS.

研究目的：本课题组既往研究显示，脂多糖（lipopolysaccharide, LPS）暴露可诱发多种疾病行为体征，包括进食量减少、体质量增长受抑、厌饮症，以及鼓膜温度呈现双相变化：先出现低体温阶段，随后鼓膜温度升高。LPS可触发一系列非特异性宿主应答，涵盖免疫应答，并可导致锌水平降低。此外，雌雄个体间的免疫应答存在差异，尤以发热表现为著，性激素可对体温调控产生干扰。本研究旨在探究锌干预对暴露于既往报道可诱发疾病行为的LPS剂量的未交配雌性Wistar大鼠的鼓膜温度、体质量增长、摄食与饮水行为，以及旷场（open field）总活动度的影响。

实验方法：将未交配雌性Wistar大鼠分为生理盐水（saline, S）组与LPS组。造模给药1小时后，生理盐水组再次给予生理盐水注射（记为S+S组）；LPS组大鼠分为两亚组，半数给予生理盐水注射（记为LPS+S组），另一半给予锌干预（记为LPS+Zn组）。连续96小时监测大鼠鼓膜温度、体质量、摄食量与饮水量，并于LPS给药后2小时开始各项观测与指标采集。

实验结果：锌干预可缓解LPS诱导的体温升高，抑制体质量增长与摄食量，同时增加大鼠饮水量。

研究结论：锌干预可有效降低LPS诱导的鼓膜温度升高，对LPS引发的其余疾病行为无显著影响。