1,2-二氯乙烷亚急性暴露对大鼠抑郁样行为及单胺神经递质水平的影响
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摘要
目的探讨1,2-二氯乙烷(1,2-DCE)亚急性暴露对大鼠抑郁样行为的影响及其可能单胺神经递质的作用机制。方法无特定病原体级雄性SD大鼠随机分为对照组和低、中、高剂量组,每组10只,分别予0、20、40、80 mg/kg体质量的1,2-DCE(以玉米油稀释)灌胃染毒,每2天1次,连续染毒14次。染毒结束后,采用旷场实验、糖水偏爱实验和强迫游泳实验观察大鼠行为学变化情况,采用高效液相色谱-电化学检测法测定大鼠大脑前额皮层、海马、纹状体中单胺类神经递质5-羟色胺(5-HT)、去甲肾上腺素(NA)和多巴胺水平。结果与对照组比较,中、高剂量组大鼠直立次数、中心区域活动时间和路程均减少(P<0.05),糖水偏爱度下降(P<0.05),强迫游泳实验中不动时间延长(P<0.05)。大鼠前额皮层、海马、纹状体内5-HT、NA和多巴胺水平均随着1,2-DCE染毒剂量的增加而下降(P<0.05),呈剂量-效应关系。高剂量组大鼠前额皮层、海马、纹状体内5-HT、NA和多巴胺水平均低于对照组(P<0.05)。结论 1,2-DCE亚急性暴露可诱导大鼠抑郁样行为,其机制可能与降低前额皮层、海马、纹状体内单胺类神经递质的水平相关。
Objective To investigate the effects of 1,2-dichloroethane(1,2-DCE) subacute exposure on depression in rats as well as the relevant mechanism of monoamine neurotransmitters. Methods The specific pathogen free male SD rats were randomly divided into control group, low-, medium-, and high-dose groups, with 10 rats in each group. The rats in these 4 groups were intra-gastrically administered with 1,2-DCE(diluted in corn oil) at the dose of 0, 20, 40, 80 mg/kg body weight, every other day for 14 times. After exposure, the behavior change of rats was observed by open-field test, sucrose preference test and forced swim test. The levels of the monoamine neurotransmitters including 5-hydroxytryptamine(5-HT), noradrenaline(NA) and dopamine(DA) in prefrontal cortex, hippocampus, and striatum of rats were analyzed by high performance liquid chromatography-electrochemical detection method. Results The number of rearing, time and distance of central area, sucrose preference index of mice in medium and high dose groups were decreased(P<0.05), while immobility time of forced swim test was increased(P<0.05) when compared with the mice in control group. The levels of 5-HT, NA and DA in prefrontal cortex, hippocampus, and striatum decreased with the increase of 1,2-DCE exposure(P<0.05), showing a dose-effect relationship. The levels of 5-HT, NA and DA in prefrontal cortex, hippocampus, and striatum in the high-dose group were lower than that of control group(P<0.05). Conclusion The subacute exposure of 1,2-DCE can induce depression-like behavior in rats. The mechanism might be related to the reduction of monoamine neurotransmitters in striatum, hippocampus and prefrontal cortex.
Objective To investigate the effects of 1,2-dichloroethane(1,2-DCE) subacute exposure on depression in rats as well as the relevant mechanism of monoamine neurotransmitters. Methods The specific pathogen free male SD rats were randomly divided into control group, low-, medium-, and high-dose groups, with 10 rats in each group. The rats in these 4 groups were intra-gastrically administered with 1,2-DCE(diluted in corn oil) at the dose of 0, 20, 40, 80 mg/kg body weight, every other day for 14 times. After exposure, the behavior change of rats was observed by open-field test, sucrose preference test and forced swim test. The levels of the monoamine neurotransmitters including 5-hydroxytryptamine(5-HT), noradrenaline(NA) and dopamine(DA) in prefrontal cortex, hippocampus, and striatum of rats were analyzed by high performance liquid chromatography-electrochemical detection method. Results The number of rearing, time and distance of central area, sucrose preference index of mice in medium and high dose groups were decreased(P<0.05), while immobility time of forced swim test was increased(P<0.05) when compared with the mice in control group. The levels of 5-HT, NA and DA in prefrontal cortex, hippocampus, and striatum decreased with the increase of 1,2-DCE exposure(P<0.05), showing a dose-effect relationship. The levels of 5-HT, NA and DA in prefrontal cortex, hippocampus, and striatum in the high-dose group were lower than that of control group(P<0.05). Conclusion The subacute exposure of 1,2-DCE can induce depression-like behavior in rats. The mechanism might be related to the reduction of monoamine neurotransmitters in striatum, hippocampus and prefrontal cortex.
引文
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[28] 韩远山,蔺晓源,易刚强,等.复方柴金解郁片对慢性应激抑郁大鼠HPA轴及海马单胺神经递质的影响[J].湖南中医药大学学报,2017,37(3):240-244.
[29] ZHANG F F,PENG W,SWEENEY J A,et al.Brain structure alterations in depression:psychoradiological evidence[J].CNS Neurosci Ther,2018,24(11):994-1003.
[2] 江嘉欣,陈嘉斌,黄丽屏,等.《职业性急性1,2-二氯乙烷中毒的诊断》修订说明[J].中国职业医学,2019,46(1):98-101.
[3] 夏丽华,黄家文,邓小峰,等.职业性急性1,2-二氯乙烷中毒3例死亡病例分析[J].中国职业医学,2018,45(5):601-605.
[4] ZHAO X E,HE Y,LI M,et al.Analysis of amino acid and monoamine neurotransmitters and their metabolites in rat urine of Alzheimer's disease using in situ ultrasound-assisted derivatization dispersive liquid-liquid microextraction with UHPLC-MS/MS[J].J Pharm Biomed Anal,2017,135:186-198.
[5] 梁涛,徐祖才.神经递质在缺血性脑血管病的中的作用的研究进展[J].中风与神经疾病杂志,2015,32(5):478-480.
[6] CAI Z J.Progressions of sleep,memory and depression applicable to psychoanalysis:a review[J].Curr Psychiatry Rev,2016,12(3):240-246.
[7] 李佳琪,高丽,周玉枝,等.衰老性学习记忆减退相关的脑内单胺类神经递质研究进展[J].药学学报,2017,52(11):1639-1646.
[8] 伍津,宋向荣,张爱华,等.1,2-二氯乙烷对大鼠血浆中MBP、NSE和S100蛋白影响[J].中国职业医学,2016,43(5):519-524.
[9] 张聪,卢慧勤,胡楚璇,等.淫羊藿苷对慢性不可预知温和刺激诱导的大鼠抑郁行为和神经递质水平的影响[J].中国药学杂志,2018,53(15):1280-1284.
[10] SUN H,YANG Y,SHAO H,et al.Sodium arsenite-induced learning and memory impairment is associated with endoplasmic reticulum stress-mediated apoptosis in rat hippocampus[J].Front Mol Neurosci,2017,10:286.
[11] JIN X,LIAO Y,TAN X,et al.Involvement of the p38 MAPK signaling pathway in overexpression of matrix metalloproteinase-9 during the course of brain edema in 1,2-dichloroethane-intoxicated mice[J].Neurotoxicology,2018,69:296-306.
[12] WANG G,YUAN Y,GAO L,et al.Disruption of intracellular atp generation and tight junction protein expression during the course of brain edema induced by subacute poisoning of 1,2-dichloroethane[J].Front Neurosci,2018,12:12.
[13] CHEN S,ZHANG Z,LIN H,et al.1,2-Dichloroethane-induced toxic encephalopathy:a case series with morphological investigations[J].J Neurol Sci,2015,351(1/2):36-40.
[14] 张雅婷,钟怡洲,李国樑,等.1,2-二氯乙烷对NIH小鼠学习记忆的影响[J].中国职业医学,2018,45(1):1-6.
[15] 杨光谦,谭孝琼,朴杰,等.1,2-二氯乙烷的体内代谢对小鼠脑水肿形成的影响[J].中国工业医学杂志,2016,29(4):298-300.
[16] PERALS D,GRIFFIN A S,BARTOMEUS I,et al.Revisiting the open-field test:what does it really tell us about animal personality?[J].Anim Behav,2017,123:69-79.
[17] LIU M Y,YIN C Y,ZHU L J,et al.Sucrose preference test for measurement of stress-induced anhedonia in mice[J].Nat Protoc,2018,13(7):1686-1698.
[18] FERNàNDEZ-GUASTI A,OLIVARES-NAZARIO M,REYES R,et al.Sex and age differences in the antidepressant-like effect of fluoxetine in the forced swim test[J].Pharmacol Biochem Behav,2017,152:81-89.
[19] 罗晓丽,黄丽丽,陈月禄,等.苯系物职业暴露人群心理健康状况初步分析[J].中华全科医学,2013,11(1):101-102,110.
[20] 胡璐璐.正己烷对人外周血淋巴细胞DNA损伤的人群调查及神经行为功能测试研究[D].杭州:浙江大学,2012.
[21] 胡函文.1,2-二氯乙烷中毒性脑病高压氧治疗研究及神经心理评估[D].广州:广州医科大学,2014.
[22] 何海然,薛占霞.抑郁症相关发病机制的研究进展[J].神经药理学报,2016,6(2):20-25.
[23] 马春燕,张晨.抑郁症神经炎症机制研究进展[J].中国医药导报,2017,14(14):33-35.
[24] 王珑,王实涛.抑郁症氧化应激发病机制及针刺治疗研究进展[J].针灸临床杂志,2017,33(11):76-80.
[25] 杨振博,姚建平,封银曼.老年抑郁症的病因病机及治疗进展[J].光明中医,2017,32(7):1066-1069.
[26] 罗国帅,杨建立,王承展,等.双歧杆菌对大鼠抑郁样行为及单胺神经递质的影响[J].天津医科大学学报,2016,22(5):401-405.
[27] 罗国帅,杨建立,司纪剑,等.N-乙酰半胱氨酸对抑郁模型大鼠行为及神经递质的影响[J].天津医药,2016,44(9):1084-1088.
[28] 韩远山,蔺晓源,易刚强,等.复方柴金解郁片对慢性应激抑郁大鼠HPA轴及海马单胺神经递质的影响[J].湖南中医药大学学报,2017,37(3):240-244.
[29] ZHANG F F,PENG W,SWEENEY J A,et al.Brain structure alterations in depression:psychoradiological evidence[J].CNS Neurosci Ther,2018,24(11):994-1003.