人参总皂苷对后肢悬吊大鼠奖励性操作式条件反射能力的保护作用

董李晋川; 陈颖; 胡秦; 鲍余; 潘瑞乐; 曾桂荣; 彭博; 刘新民; 石哲

doi:10.1016/j.dcmed.2024.01.005

人参总皂苷对后肢悬吊大鼠奖励性操作式条件反射能力的保护作用

Protective effects of ginseng total saponins on reward-directed operant conditioning in hindlimb suspension rats

摘要

摘要:
目的本研究旨在探讨人参总皂苷（GTSs）对持续暴露于微重力环境导致的宇航员认知障碍的治疗作用。
方法按完成奖赏条件反射适应任务的时间，将50只无特定病原体（SPF）雄性 Wistar 大鼠随机分为对照组、后肢悬吊（HLS）组、石杉碱甲（HLS-Hup A 0.1 mg/kg）组、GTSs低剂量（HLS-GTSs 100 mg/kg）组和 GTSs高剂量（HLS-GTSs 200 mg/kg）组。除对照组外，其余各组大鼠后肢悬吊并给予药物治疗（第 20 – 58 天），进行奖赏反射测试，并对大鼠的海马进行尼氏体染色和蛋白质印迹检测。
结果造模后，与对照组比较，HLS 组大鼠按压杠杆次数减少，完成奖赏条件反射任务Ⅰ的时间延长（P < 0.05），而 HLS-GTSs 100和200 mg/kg 组大鼠上述指标无明显变化（P > 0.05）。奖赏操作条件反射Ⅱ实验中，与对照组相比，HLS 组大鼠按压杠杆次数明显减少（P < 0.05），触摸鼻腔次数明显减少（P < 0.01）；与 HLS 组大鼠比较，HLS-GTSs 100 mg/kg 组大鼠杠杆按压次数和鼻触次数均明显增加（P < 0.05），HLS-GTSs 200 mg/kg 组完成时间显著缩短，杠杆按压次数显著增加（P < 0.05）。视觉信号辨别实验中，与对照组大鼠相比，HLS 组大鼠视觉信号辨别测试指标降低（P < 0.01），HLS-GTSs 100和 200 mg/kg组大鼠视觉信号辨别能力明显升高（P < 0.01）。奖赏消退实验中，与对照组相比，HLS 组大鼠的杠杆按压次数显著增加（P < 0.01）；与 HLS 组相比，HLS-GTSs 100和 HLS-GTSs 200 mg/kg 组大鼠的杠杆按压次数显著降低（P < 0.05）。HLS 组大鼠 N-甲基-D-天冬氨酸受体 1 （NR1）和磷酸化 N-甲基-D-天冬氨酸受体 2B（p-NR2B）蛋白表达明显降低（分别为P < 0.01和P < 0.05），而 NR2B 蛋白表达无明显变化（P > 0.05）。GTSs 可上调 p-NR2B 的表达水平（P < 0.01）。
结论 GTSs通过调节NR1/NR2B磷酸化通路改善大鼠对复杂操作的学习记忆能力。

Abstract:
Objective To explore the therapeutic effects of ginseng total saponins (GTSs) on cognitive impairments in astronauts caused by prolonged exposure to microgravity environment.
Methods Fifty specific pathogen-free (SPF) male Wistar rats were randomized into control, hindlimb suspension (HLS), Huperzine A (HLS-Hup A 0.1 mg/kg), low-dose GTSs (HLS-GTSs 100 mg/kg), and high-dose GTSs (HLS-GTSs 200 mg/kg) groups, based on the completion time of reward-directed conditioning tasks. Except for rats in the control group, the others were subjected to HLS and treated with drugs (day 20 – 58), received reflex test under the condition of rewarding, and underwent Nissl body staining and Western blot detection on hippocampal.
Results After modeling, rats in HLS group exhibited a reduction in the number of lever presses and an increase in the completion time of the reward-directed operant conditioning task Ⅰ (P < 0.05) when compared with the control group, which were not substantially altered in the HLS-GTSs 100 and 200 mg/kg groups (P > 0.05). In the reward-directed operant conditioning task Ⅱ, the HLS group rats demonstrated a marked decrease in the number of lever presses (P < 0.05) and nose pokes (P < 0.01) when compared with the control group rats; the HLS-GTSs 100 mg/kg showed a significant increase in the number of lever presses and nose pokes (P < 0.05), while the HLS-GTSs 200 mg/kg demonstrated a significant reduction in completion time and an elevation in the number of lever presses (P < 0.05) when compared with the HLS group rats. In visual signal discrimination task, compared with the control group rats, the HLS group rats showed decrease in the indexes of the visual signal discrimination (P < 0.01), while HLS-GTSs 100 and 200 mg/kg groups exhibited manifest increase in it (P < 0.01). In reward extinction experiment, the number of lever presses in HLS rats significantly increased when compared with the control group (P < 0.01); compared with the HLS group, HLS-GTSs 100 and 200 mg/kg groups demonstrated a marked descrease (P < 0.05). The expressions of N-methyl-D-aspartic acid receptor 1 (NR1) and phosophorylated N-methyl-D-aspartic acid receptor 2B (p-NR2B) proteins were markedly decreased in rats in the HLS group (P < 0.05 and P < 0.01, respectively), while that of NR2B protein maintained the same (P > 0.05). GTSs increased the expression levels of p-NR2B (P < 0.01).
Conclusion GTSs improved the learning and memory ability of complex operations by regulating the NR1/NR2B phosphorylation pathways in rats.

HTML全文

参考文献(45)

施引文献

资源附件(0)