足底注射完全弗氏佐剂致疼痛抑郁共病模型大鼠行为学及单胺类神经递质改变  

Plantar injection of complete Freund’s adjuvant induces behavioral and monoamine neurotransmitter changes in comorbid pain and depression model rats

作　　者：羊璞 粟胜勇[2] 王甜 苏虹 YANG Pu;SU Shengyong;WANG Tian;SU Hong(the First School of Clinical Medicine,Guangxi University of Chinese Medicine,Nanning 530023,China;Department of Acupuncture and Moxibustion,the First Affiliated Hospital of Guangxi University of Chinese Medicine,Nanning 530023;Guangxi Key Laboratory of Molecular Biology of Preventive Medicine of Traditional Chinese Medicine,Nanning 530023)

机构地区：[1]广西中医药大学第一临床医学院,南宁530023 [2]广西中医药大学第一附属医院针灸科,南宁530023 [3]广西中医药防治医学分子生物重点实验室,南宁530023

出　　处：《中国实验动物学报》2023年第11期1408-1414,共7页Acta Laboratorium Animalis Scientia Sinica

基　　金：国家自然科学基金(81960895,82160934);广西壮族自治区一流学科建设项目(2018XK075);广西中医药大学研究生教育创新计划项目(YCBXJ2023023)。

摘　　要：目的观察足底注射完全弗氏佐剂对大鼠疼痛抑郁行为的影响及海马单胺类神经递质的变化,旨在建立慢性炎性疼痛抑郁共病动物模型。方法将16只8周龄SPF级健康雄性SD大鼠随机分为模型组与对照组,每组8只。模型组大鼠麻醉后通过左后足底注射完全弗氏佐剂100μL,建立慢性炎性疼痛抑郁共病模型大鼠,对照组注射同体积生理盐水。采用Von Frey纤维丝和热辐射刺激仪测量大鼠的疼痛阈值,采用旷场实验、悬尾实验、强迫游泳实验评价大鼠的抑郁行为,采用酶联免疫吸附实验检测大鼠海马组织的5-羟色胺、多巴胺、去甲肾上腺素的含量,采用苏木精-伊红(HE)染色观察大鼠海马区病理改变。结果与对照组相比,模型组大鼠机械缩足阈值及热缩足反射潜伏期在3、7、14 d明显降低(P<0.01);与对照组相比,模型组大鼠旷场实验运动总距离在7、14 d明显减少(P<0.01),中央区停留时长在14 d明显降低(P<0.01);与对照组相比,模型组大鼠悬尾实验不动时间在14 d明显增加(P<0.01);与对照组相比,模型组大鼠强迫游泳实验不动时间在7、14 d明显增加(P<0.05,P<0.01);与对照组相比,模型组大鼠海马中5-羟色胺、多巴胺、去甲肾上腺素含量明显减少(P<0.01)。与对照组相比,模型组大鼠海马组织病理发生改变,神经元形态不规则,排列松散、紊乱,细胞间隙增大,部分细胞核模糊,出现部分神经元固缩、凋亡。结论100μL完全弗氏佐剂足底注射可引起大鼠痛觉过敏、抑郁样行为改变及海马单胺类神经递质明显降低,造成海马病理形态变化,可有效模拟疼痛抑郁共病的表现,是一种可用于慢性炎性疼痛抑郁共病病理机制研究的实验模型。Objective To observe the effects of plantar injection of complete Freund's adjuvant(CFA)on pain-depressive behavior and changes in hippocampal monoamine neurotransmitters in rats to establish an animal model of related comorbidity.Methods Sixteen male,8-week-old,SPF-grade healthy SD rats were randomly divided into model and control groups with eight rats in each group.In the model group,rats were anesthetized and injected with 100 μL CFA in the left hind paw to induce the comorbid chronic inflammatory pain and depression model.In the control group,rats were injected with the same volume of saline.Pain thresholds were measured using the Von Frey hair and thermal radiation instrument,and depression-like behaviors were assessed using the open field test(OFT),tail suspension test(TST),and forced swim test(FST).Enzyme-linked immunosorbent assays were used to measure 5-hydroxytryptamine(5-HT),dopamine(DA),and norepinephrine(NE)in rat hippocampal tissue.Histological changes in the hippocampal area were observed by hematoxylin-eosin(HE) staining.Results Compared with the control group,the mechanical withdrawal threshold and thermal withdrawal latency in the model group were significantly decreased at 3,7,and 14 days(P < 0.01).The total distance in the OFT was significantly reduced at 7 and 14 days(P < 0.01),and the time spent in the center zone was significantly decreased at 14 days(P < 0.01).Immobility time in the TST was significantly increased at 14 days(P < 0.01),and the immobility time in the FST was significantly increased at 7 and 14 days(P < 0.05,P < 0.01).5-HT,DA,and NE contents in hippocampal tissue of the model group rats were significantly reduced compared with those in the control group(P < 0.01),and hippocampal tissue in the model group showed pathological changes,including irregular neuronal shapes,loose and disordered arrangement,increased intercellular space,some unclear cell nuclei,and some neuronal contraction and apoptosis.Conclusions Injection of 100 μL CFA into the footpad causes pain hypersensiti

关 键 词：疼痛 抑郁 共病 完全弗氏佐剂 单胺类神经递质 大鼠 动物模型 

分 类 号：Q95-33[生物学—动物学]