阿魏酸钠对谷氨酸盐诱导的成年小鼠神经毒性的保护作用

Potent protective effect of ferulic acid on glutamate-induced neurotoxicity in adult mice

目的研究阿魏酸钠（sF）对谷氨酸单钠（MSG）诱导的成年小鼠神经兴奋性毒性的保护作用。方法60只昆明小鼠采用数字随机表法分为对照组、SF组、MSG组、MSG＋SF组[根据SF剂量不同，又分为20、40、80mg／（kg·d）三个亚组]，每组各10只。MSG组小鼠灌胃MSG[2．0g/（kg·d）]，MSG＋SF组MSG[2．0/（kg·d）]灌胃的同时腹腔注射SF[20、40、80mg／（kg·d）]，SF组腹腔注射SF[40mg／（kg·d）1，每日1次，连续给药10d；对照组灌胃和腹腔注射同量生理盐水。通过小鼠的行为学实验和脑海马组织病理检查．分析MSG所引起的功能和形态学上的变化以及SF的保护作用。结果末次给药后第6天MSG组Y．迷宫正确反应次数比例（13．80／20）显著少于对照组（16．42／20），差异有统计学意义（P〈0．01）；MSG[2．0g/（k·d）】＋SF[（40mg／（kg·d）]维Y-迷宫正确反应次数比例（16．30／20）与对照组差异无统计学意义胗0．05）。MSG组小鼠海马细胞水肿、神经元变性坏死和组织增生；MSG[2．0g／（kg·d）】＋SF【（40mg／（kg·d）]组海马未发现明显的组织病理学改变。结论SF能部分抵消MSG诱导的成年小鼠行为障碍和脑海马病理组织损伤；SF对MSG诱导的成年小鼠神经兴奋性毒性存在保护作用。

Objective To investigate a possible protective effect of sodium ferulate （SF） on monosodium glutamate （MSG）-induced neurotoxicity in adult mice. Methods Sixty mice were randomly divided into control, SF, MSG, and MSG ＋ SF [ 20, 40, 80 mg/（kg.d）] groups, n=10. The animals in MSG group received intragastric （ig） administration of MSG （2.0 g/（kg, d）], the animals in the MSG＋SF groups received simultaneously ig administration of MSG [2.0 g/（kg·d）] and intraperitoneal （ip） administration of SF [ 20, 40, 80 mg/（kg· d）], the animals in SF group received ip administration of SF [40 mg/ （kg·d）], and the animals in control group received ig and ip administration of normal saline, respectively, once-daily for 10 d. On day 1 after the last ig administration of MSG or （and） SF the behavioural tests （test of Y-maze discrimination learning and open field test） were performed, and on day 4 after the treatment of MSG or （and） SF the histopathology of the animal brains was studied to analyze the MSG-induced functional and morphological changes and the possible protective effect of SF. Results The correct responses of Y-maze test on day 6 after the last administration of MSG and / or SF in MSG-treated group （13.83/20） were significantly less than those in control （16.42/20）（P〈0.01）, and those in MSG[2.0 g/（kg ·d）]＋SF[40 mg/（kg .d）]-treated mice （16.30/20） were close to those in control （P〉0.05）. Examination of histopathology displayed MSG-treated hippocampal lesions characterized by intracellular edema, degeneration and necrosis of neurons, and hyperplasia, and the hippocampal lesion did not appear in the MSG[2.0 g/（kg.d）]＋SF[40 mg/（kg.d）]-treated mice. Conclusions SF partially countered the behavior disorders and hippocampal lesions induced by MSG; therefor, SF has a potent neuroprotection against MSG-induced neurotoxicity in adult mice.