桂枝加葛根汤对脂多糖诱导神经炎症小鼠学习记忆障碍的改善作用

目的研究桂枝加葛根汤（GuizhiplusGegenDecoction，GGD）对脂多糖（Jjpop0Iysaccha卜ides，LPS）诱导神经炎症小鼠学习记忆的影响及可能的作用机制。方法63只雄性ICR小鼠随机分为5组：正常对照组（正常纽，13只）、神经炎症模型组（模型组，13只）、桂枝加葛根汤低剂量组（GGD低组，10只）、桂枝加葛根汤高剂量组（GGD高组，14只）、阳性对照组（对照组，13只）。给予小鼠腹腔注射LPS（0．33mg／kg）建立阿尔茨海默氏病（Alzheimer’Sdisease，AD）的神经炎症模型；GGD低组（6g／kg）和GGD高组（12g／kg）给予GGD灌胃治疗共4周；阳性对照组给予二甲基四环素（50mg／kg）腹腔注射共3天，药物治疗结束后每天行为学测试前4h注射LPS造模，然后5组小鼠同时进行行为学测试，分别采用旷场实验、新异物体识别任务和Morris水迷宫观察GGD对神经炎症小鼠学习记忆的影响。结果旷场实验显示各组小鼠之间的活动时间及活动距离差异无统计学意义（P〉0．05），LPS及GGD对小鼠的活动能力均没有产生影响；新异物体识别任务显示，LPS诱导后小鼠对新物体的探索时间明显缩短（P〈0．05），而GGD低组和GGD高组小鼠的探索能力及记忆保持能力明显改善（P〈0．05，P〈0．01）；Morris水迷宫结果显示，LPS诱导后小鼠的逃避潜伏期明显延长（P〈0．05），穿越原平台的游泳时间百分比明显减少（P〈0．05），GGD低组和GGD高组小鼠逃避潜伏期均明显缩短，游泳时间百分比明显增加（P〈0．05，P〈0．01）。结论GGD对LPS诱导的神经炎症小鼠学习记忆障碍具有一定程度的改善作用。

Enhanced Effect of Guizhi plus Gegen Decoction on Learning and Memory Disorder in LPS Induced Neuroinflammatory Mice

Objective To explore the potential effect of Guizhi plus Gegen Decoction （GGD） in improving learning and memory of lipopolysaccharides （LPS） induced neuroinflammatory mice and its possible mechanisms. Methods Totally 63 male ICR mice were randomly divided into 5 groups, i.e., the normal control （n =13）, the model group （n =13）, the low dose GGD group （n =10）, the high dose GGD group （n = 14）, and the positive control group （n = 13）. Mice were intraperitoneally injected with LPS （0.33 mg/kg） to induce Alzheimer＇s disease （AD） model. Mice in the high and the low dose GGD groups were administered with 12 g/kg or 6 g/kg by gastrogavage for 4 successive weeks. Mice in the control group were intraperitoneally injected with minocycline （50 mg/kg） for 3 days. By the end of treatment LPS were injected 4 h before behavior test each day, and then behavior test was conducted in mice of each group. Effect of GGD on learning and memory of AD mice was observed by using open field test, novel object recognition task, and Morris water maze. Results Open field test showed there was no statisticaldifference in the movement time and the movement distance among all groups （P 〉0.05）, suggesting that LPS and GGD had no effect on locomotor activities of mice. In novel object recognition test, AD mice spent significantly shorter time to explore novel object after they were induced by LPS （P 〈0.05）, while for AD mice in the low and high dose GGD groups, their capacities for exploration and memory were sig- nificantly improved （P 〈0.05, P 〈0.01 ）. Results of Morris water maze showed that AD mice exhibited in- creased escape latency （P 〈0.05） and spent much less time in swimming across the original platform （both P 〈0.05）. However, AD mice in the low and high dose GGD groups had obvious shortened latency and increased time percentage for swimming （P 〈0.05, P 〈0.01 ）. Conclusion GGD possessed certain improvement in learning and memory disorder of LPS induced AD mice.