锌对孕期暴露脂多糖Wistar大鼠雌性成年子代行为的影响及其机制

目的：探讨硫酸锌（ZnSO4）注射液对孕期暴露于脂多糖（lipopolysaccharides，LPS）大鼠雌性成年子代的行为、神经免疫功能的影响及其机制。方法：随机将15 只孕期（孕期0～9.5 d）Wistar大鼠分为3 组，分别注射LPS和ZnSO4（LPS＋Zn组）、LPS和无菌生理盐水（saline，SAL）（LPS＋SAL组）、SAL和SAL（SAL＋SAL组）。产后81～86 d，从每窝选取2～3 只雌性成年子代（10～12 只/组），动情间期将大鼠放置在抑制性应激反应管道2 h，在最后5 min，播放不同音频的超声波，记录大鼠保持寂静的时间（寂静期）。超声波测试后，立即将雌性成年子代放置在开放场域中，测定其运动和焦虑状态。开放场域行为测试后，立即取大鼠躯干血，采用酶联免疫吸附实验（enzyme-linked immunosorbent assay，ELISA）测定血清皮质酮、脑源性神经营养因子（brain-derivedneurotrophic factor，BDNF）水平；采用高效液相色谱法（high performance liquid chromatography，HPLC）测定大鼠下丘脑和纹状体的单胺及其代谢产物水平。结果：与LPS＋SAL组、SAL＋SAL组相比，LPS＋Zn组的雌性成年子代大鼠呈现最大音频寂静持续时间延长（P＜0.05或P＜0.01）、行走距离延长（P＜0.05或P＜0.001）、平均速率加快（P＜0.05或P＜0.001）、自我梳理时间缩短（P＜0.001或P＜0.01）、纹状体去甲肾上腺素代谢率降低（P＜0.05或P＜0.01）的特征。与LPS＋SAL组相比，LPS＋Zn组大鼠的血清皮质酮水平降低（P＜0.05）。结论：ZnSO4注射液作用于孕期遭受感染或炎症的母体，在急性抑制应激期后，其雌性成年子代应激反应减轻。即孕期为感染的母体注射ZnSO4也许是一个潜在的、有益的保护其子代行为的防治措施。

Effect and Underlying Mechanism of Prenatal Zinc Treatment on Stress Response in Adult Female Wistar Rat Offspring Exposed to Lipopolysaccharide during Pregnancy

Objective: To explore the effects and underlying mechanisms of prenatal zinc treatment (zinc sulfate injection)
for pregnant rats exposed to lipopolysaccharide on the behavior and neuroimmune system of their adult female offspring.
Methods: Totally 15 Wistar rats were divided into 3 groups randomly and injected with lipopolysaccharide (LPS) plus zinc
sulfate (LPS + Zn), LPS plus sterile saline (SAL) (LPS + SAL), and SAL plus SAL (SAL + SAL), respectively. Two or
three female offspring during postnatal days 81–86 (n = 10–12 per group) were chosen. The offspring that were in diestrus
or metestrus were placed in a restraint stress tube for 2 hours. In the final 5 min of restraint stress, they were subjected
to different ultrasonic vocalizations. The behavioral duration times and silence duration times were recorded. After the
ultrasonic vocalization test, the rats were removed from the restraint tube and observed in an open field to evaluate motor and
anxiety parameters immediately. Immediately after the open field test, trunk blood was collected in conical tubes, and serum
corticosterone levels and brain derived neurotropic factor were evaluated by enzyme-linked immunosorbent assay (ELISA).
The levels of monoamine and their turnover in the hypothalamus and striatum were determined by high-performance liquid
chromatography (HPLC). Results: Longer silence time (P < 0.05, P < 0.01), longer travel distance (P < 0.05, P < 0.001),
faster average response speed (P < 0.05, P < 0.001), shorter self-grooming time (P < 0.001, P < 0.01), and lower
metabolic rate of norepinephrine in striatum (P < 0.05, P < 0.01) in the LPS + Zn group were observed when compared
with the LPS + SAL and SAL + SAL groups. Lower levels of serum corticosterone (P < 0.05) in the LPS + Zn group
were also found when compared with the LPS + SAL group. Conclusion: Prenatal zinc treatment has a potential
beneficial effect on adult female rat offspring stricken with infectious/inflammatory processes during gestation by
reducing the stress response.