吴茱萸次碱对脂多糖致小鼠神经炎症和认知功能障碍的作用研究

Rutaecarpine Protects Mice from Lipopolysaccharide-Induced Neuroinflammation and Cognitive Impairment

目的研究吴茱萸次碱对脂多糖诱发的C57BL/6N小鼠学习记忆障碍的改善作用及其作用机制探讨。方法将54只7周龄C57BL/6N小鼠经水迷宫筛选合格后按随机数字表法分为对照组、模型组、多奈哌齐组、吴茱萸次碱低、中、高剂量组。除正常组注射等体积生理盐水外,其他组腹腔注射2 mg/kg脂多糖溶液。造模成功后,正常组和模型组给予等体积0.9%生理盐水,多奈哌齐组给予5 mg/kg多奈哌齐、吴茱萸次碱低、中、高剂量组分别给予0.97 mg/kg、3.03 mg/kg、9 mg/kg吴茱萸次碱。连续给药2周后,以Morris水迷宫评价小鼠空间记忆能力。取脑进行HE和Tunel染色并以试剂盒测定脑组织中TNF-α、MDA、GSH-PX、GSH、IL-6、IL-10水平。结果与对照组比较,模型组C57BL/6N小鼠穿台次数明显减少,上台时间和距离明显增加,TNF-α、MDA、IL-6、IL-10水平明显升高,GSH-px和GSH水平和海马神经细胞明显减少。与模型组比较,5 mg/kg多奈哌齐和0.97 mg/kg、3.03 mg/kg、9.00 mg/kg吴茱萸次碱给药后使穿越平台次数明显增加,上台时间和距离明显降低,使脑内TNF-α、MDA、IL-10、IL-6水平明显降低,减少神经细胞的损伤,而5 mg/kg多奈哌齐和3.03 mg/kg、9.00 mg/kg吴茱萸次碱给药使GSH-px、GSH明显升高。结论吴茱萸次碱可以通过下调大脑内的炎症反应、氧化应激及修复海马的损伤来改善C57BL/6N小鼠的学习记忆障碍。

Objective To investigate the effect and mechanism of rutaecarpine in mitigating the learning and memory impairment induced by lipopolysaccharide in C57BL/6N mice.Methods Fifty-four 7-week-old C57BL/6N mice were selected and qualified by Morris water maze and assigned by the random number table method into 6 groups:normal,model,donepezil(5 mg/kg),and low-,medium-,and high-dose(0.97,3.03,and 9.00 mg/kg,respectively)rutaecarpine.Except that the normal group received injection of equal volume of normal saline,other groups received intraperitoneal injection of 2 mg/kg lipopolysaccharide solution for modeling.After the successful modeling,mice in the normal and model groups were administrated with 0.9%normal saline,and those in other groups with corresponding drugs.Two weeks later,Morris water maze test was conducted to evaluate the memory of mice in each group.The hippocampus was collected and stained with hematoxylin-eosin and terminal-deoxynucleoitidyl transferase-mediated nick-end labeling.The levels of tumor necrosis factor(TNF)-α,malondialdehyde(MDA),glutathione peroxidase(GSH-PX),glutathione(GSH),interleukin(IL-6),and IL-10 in the hippocampus were determined by kits.Results Compared with the normal group,the model group showed decreased times of crossing the platform,increased time and distance on the platform,elevated levels of TNF-α,MDA,IL-6,and IL-10,lowered levels of GSH-PX and GSH,and reduced hippocampal neurons.Compared with the model group,5 mg/kg donepezil and 0.97,3.03,and 9.00 mg/kg rutaecarpine increased the times of crossing the platform,reduced the time and distance on the platform,lowered the levels of TNF-α,MDA,IL-10,and IL-6,and reduced neuronal damage.In addition,5 mg/kg donepezil and 3.03 and 9.00 mg/kg rutaecarpine elevated the levels of GSH-PX and GSH.Conclusion Rutaecarpine can mitigate the learning and memory impairment of C57BL/6N mice by reducing inflammation and oxidative stress and repairing hippocampal damage in the brain.