γ-氨基丁酸对DEHP染毒大鼠焦虑行为的干预研究
Intervention effect of Gamma aminobutyric acid on anxiety behavior induced by di(2-ethylhexyl) phthalate in rats
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摘要: 目的:研究γ-氨基丁酸(GABA)对邻苯二甲酸二(2-乙基己基)酯(DEHP)染毒大鼠焦虑行为的影响。方法:将30只雄性SD大鼠随机分为5组:对照组(C)、DEHP组(500 mg/kg)、GABA低、中、高剂量干预组(L组:500 mg/kg DEHP+1 mg/kg GABA、M组:500 mg/kg DEHP+2 mg/kg GABA、H组:500 mg/kg DEHP+4 mg/kg GABA),连续干预30 d。利用高架十字迷宫(EPM)测定干预前后大鼠行为变化,随后测定大鼠额叶皮质五羟色胺(5-HT)、去甲肾上腺素(NE)的水平。结果:干预前各组大鼠EPM指标无显著性差异(p>0.05);干预后H组和C组总食物利用率显著高于DEHP组(p<0.05);干预后各组大鼠入臂总次数无显著性差异(p>0.05),DEHP组大鼠开臂时间百分比、开臂次数百分比均极显著低于对照组(p<0.01),M组和H组开臂时间百分比及开臂次数百分比均显著高于DEHP组(p<0.05);DEHP组5-HT和NE均显著高于C组(p<0.05),M组5-HT及NE均显著低于DEHP组(p<0.05),H组5-HT及NE均极显著低于DEHP组(p<0.01)。结论:DEHP可能通过升高额叶皮质5-HT、NE水平造成大鼠焦虑,GABA可以通过降低额叶皮质5-HT、NE水平起到改善焦虑的作用。Abstract: Objective : To investigate the effect of γ- aminobutyric acid( GABA) on the neurobehavior of rats induced by di(2-ethylhexyl) phthalate(DEHP). Methods:30 male Sprague-Dawley rats were divided into 5groups randomly:control group,DEHP group(500 mg/kg DEHP),low GABA group(L:500 mg/kg DEHP and1 mg/kg GABA),medium GABA group(M :500 mg/kg DEHP and 2 mg/kg GABA),and high GABA group(H:500 mg/kg DEHP and 4 mg/kg GABA). The interventions for DEHP exposure continued for 30 consecutive days. Behavioral changes of rats before and after interventions were assessed in the elevated plus maze test(EPM),and the levels of serotonin(5-HT) and norepinephrine(NE) in prefrontal cortex of rats were measured.Results:No significant differences were found in the EPM among the five groups(p>0.05) before interventions.DEHP and GABA treatment had no significant effects on the body weight of rats. The total food utilization rate of H group and C group were higher than DEHP group(p <0.05). The total entrance was not significantly different among different groups(p>0.05) after interventions. DEHP group had decreased percentage of time spent in open arms and entrance frequency to open arms than C group in the EPM test(p<0.01). The percentage of time spent in open arms and entrance frequency to open arms of M and H group were higher than DEH Pgroup(p<0.05). The levels of 5-HT and NE of DEHP group were higher than C group(p<0.05). The levels of5-HT and NE of M group were lower than DEHP group(p<0.05). The levels of 5-HT and NE of H group were lower than DEHP group(p<0.01). Conclusion:DEHP elevated 5-HT and NE levels in prefrontal cortex of rats and induces anxiety of rats. However,these effects induced by DEHP could be alleviated under GABA intervention through reducing 5-HT and NE in prefrontal cortex of rats.