摘要
目的:探究裙带菜多糖(UPPs)对慢性不可预见性温和应激(CUMS)处理大鼠抑郁样行为及单胺类神经递质含量、氧化应激和下丘脑-腺垂体-肾上腺(HPA)轴的影响.方法:利用CUMS方法制备大鼠抑郁症模型,使用灌胃方法分别给予大鼠生理盐水(NS)、不同剂量UPPs干预.观察大鼠的一般状况并通过旷场试验(OFT)、糖水偏好试验(SPT)、强迫游泳试验(FST)检测大鼠的抑郁样行为,通过商品化试剂盒检测大鼠海马或血清中5-羟色胺(5-HT)、多巴胺(DA)和去甲肾上腺素(NE)、丙二醛(MDA)、超氧化物岐化酶(SOD)和过氧化氢酶(CAT)、促肾上腺皮质激素(ACTH)、皮质酮(CORT)活性或者水平,利用Western Blot法检测海马糖皮质激素受体(GR)蛋白的表达水平,利用苏木精-伊红(HE)染色观察大鼠海马的组织结构.结果:UPPs中、高剂量组大鼠抑郁样行为明显改善(P<0.05),UPPs高剂量组大鼠的海马5-HT、DA、NE含量均有提高(P<0.05),血清和海马的MDA含量均有降低(P<0.05)、SOD和CAT活性均有提高(P<0.05),血清ACTH、CORT含量均有降低(P<0.05);UPPs中剂量组海马MDA、CAT,血清SOD、ACTH、CORT均有改善(P<0.05);海马GR蛋白表达水平提升(P<0.05);海马齿状回病理改变明显改善.结论:UPPs能减轻CUMS大鼠的抑郁样行为,其作用机制可能与提高海马单胺类神经递质含量、减轻氧化应激损伤和HPA轴亢进有关.
Abstract
Objective:To explore the effects of Undaria pinnatifida polysaccharides(UPPs)on depressive-like behavior,neurotransmitter content,oxidative stress,and the hypothalamus-pituitary-adrenal(HPA)axis in rats treated with chronic unpredictable mild stress(CUMS).Methods:A rat model of depression was prepared using the CUMS method,and rats were treated with normal saline(NS)or different doses of UPPs by gavage.The general condition of the rats was observed,and depressive-like behavior was detected by the open field test(OFT),sucrose preference test(SPT),and forced swimming test(FST).The activity or levels of 5-hydroxytryptamine(5-HT),dopamine(DA)and norepinephrine(NE),malondialdehyde(MDA),superoxide disidase(SOD)and catalase(CAT),adrenocorticotrop-ic hormore(ACTH),corticosterone(CORT)in the hippocampus or serum of rats were detected using commercial kits.Western Blot was used to detect the expression level of hippocampal glucocorticoid receptor(GR)protein,and hema-toxylin-eosin(HE)staining was used to observe the tissue structure of hippocampus of rats.Results:The depressive-like behavior of rats in the UPPs medium and high dose groups was significantly improved(P<0.05).In the UPPs high dose group,the contents of 5-HT,DA,and NE in the hippocampus of rats increased(P<0.05),while the con-tents of MDA in both serum and hippocampus decreased(P<0.05),and the activities of SOD and CAT increased(P<0.05).The contents of ACTH and CORT in serum decreased(P<0.05).In the UPPs medium dose group,the levels of hippocampal MDA and CAT,as well as serum SOD,ACTH,and CORT were improved(P<0.05).The expression level of GR protein in the hippocampus increased(P<0.05),and the pathological changes in the hipp-ocampal dentate gyrus were significantly improved.Conclusion:UPPs can alleviate depressive-like behavior in CUMS rats,and its mechanism may be related to increasing the content of monoamine neurotransmitters in the hippocampus,reducing oxidative stress damage,and HPA axis hyperfunction.
基金项目
福建省自然科学基金(2020J01609)
福建医科大学国家级大学生创新训练项目(201610392012)