摘要
目的研究加味礞石滚痰汤对非自杀性自伤行为模型小鼠行为学以及腹侧被盖区(ventral tegmental area,VTA)多巴胺能神经元的影响,并探讨其疼痛调控机制。方法选取36只雄性小鼠随机分为正常组、模型组、舍曲林组及加味礞石滚痰汤高、中、低剂量组,每组6只。正常组不予刺激,其余5组应用慢性不可预见温和应激(chronic unpredictable mild stress,CUMS)的方法制备模型。造模同时灌胃给药,加味礞石滚痰汤高、中、低剂量组和舍曲林组分别予以对应药物灌胃治疗,正常组、模型组给予等剂量生理盐水灌胃。采用悬尾实验评价小鼠行为学指标;ELISA法检测VTA及杏仁核中多巴胺(dopamine,DA)、多巴胺转运体(dopamine transporter,DAT)及酪氨酸羟化酶(tyrosine hydroxylase,Th)含量;蛋白免疫印迹法检测VTA及杏仁核中DAT、Th含量。结果应激6周后,模型组小鼠不动时间明显增长,糖水偏好率明显下降。ELISA结果显示,模型组小鼠VTA和杏仁核中DA、Th含量显著下降(P<0.01),DAT表达增加(P<0.01);蛋白免疫印迹法(Western Blot,WB)结果显示,模型组小鼠VTA和杏仁核中DAT表达增加(P<0.01),Th的含量降低(P<0.01)。给药后,加味礞石滚痰汤中、高剂量组和舍曲林组小鼠的不动时间和糖水偏好明显提升(P<0.01)。ELISA结果显示,加味礞石滚痰汤低剂量组小鼠VTA和杏仁核中DA含量升高(P<0.05),杏仁核中DAT表达下降(P<0.05);加味礞石滚痰汤中剂量组小鼠VTA和杏仁核中DA含量升高(P<0.01),VTA中Th含量升高(P<0.01),杏仁核中DAT表达下降(P<0.01);加味礞石滚痰汤高剂量组和舍曲林组小鼠VTA和杏仁核中DA、Th含量升高(P<0.01),DAT表达下降(P<0.01)。WB结果提示,加味礞石滚痰汤各剂量组和舍曲林组小鼠VTA和杏仁核中Th含量升高(P<0.01),DAT含量下降(P<0.01)。结论加味礞石滚痰汤能够改善模型小鼠抑郁样行为和提升动机,其机制可能与增加Th含量、下调DAT表达、增加DA水平有关。
Objective To investigate the effects of Jiawei Megnshi Guntan Decoction on behavioral responses and the function of dopamine(DA)neurons in the ventral tegmental area(VTA)of rats modeled with non-suididal self-injury,and to explore its mechanisms of pain regulation.Methods Thirty-six male rats were randomly divided into six groups:a normal group,model group,Jiawei Mengshi Guntan Decoction group(high dose,medium dose,low dose),and Sertraline group,with six rats in each group.The normal group was not stimulated,while the remaining five groups were given chronic unpredictable mild stress(CUMS)to establish the model.Drugs was administered through gastric gavage at the same time as molding.The Chinese medicine group and the sertraline group were given Jiawei Mengshi Guntan Decoction and sertraline respectively,while the normal group and the model groups received equivalent doses of saline.Behavioral responses were assessed using the tail suspension test.The contents of DA,dopamine transporter(DAT)and tyrosine hydroxylase(Th)in VTA and amygdala were determined by ELISA.The contents of DAT and Th in VTA and amygdala were determined by Western Blot.Results After 6 weeks of stress,CUMS rats exhibited significantly increased immobility time and decreased sucrose preference.ELISA results indicated that the contents of DA and Th in VTA and amygdala were significantly decreased(P<0.01),while the expression of DAT was increased(P<0.01).Western Blot results confirmed increased DAT expression in the VTA and amygdala increased(P<0.01),while the content of Th decreased(P<0.01).After treatment,the immobile time and sugar water preference of rats in the Chinese medicine group of high/medium dose,and sertraline groups were significantly increased(P<0.01).The ELISA results showed that the contents of DA in VTA and amygdala increased(P<0.05),while the expression of DAT in the amygdala decreased(P<0.05)in the Chinese medicine group of low does.In the Chinese medicine group of medium does,the contents of DA in VTA and amygdala increased(P<0.01),and the content of Th in VTA increased(P<0.01),while the expression of DAT in the amygdala decreased(P<0.01).In the Chinese medicine group of high does and Sertraline group,it showed that the contents of DA and Th in VTA and amygdala were increased(P<0.01),while the expression of DAT was decreased(P<0.01).WB results indicated that the contents of Th in VTA and amygdala of rats in the Chinese medicine group and Sertraline group were increased(P<0.01),while the contents of DAT decreased(P<0.01).Conclusion Jiawei Mengshi Guntan Decoction can improve depression-like behavior and enhance motivation in model rats;its mechanism may involve increasing Th content,down-regulating DAT expression and increasing DA level.
作者
丁一芸
王雅璇
王素梅
DING Yiyun;WANG Yaxuan;WANG Sumei(Department of Psychosomatic Medicine,Dongfang Hospital,Beijing University of Chinese Medicine,Beijing 100078,China)
出处
《环球中医药》
2025年第1期13-19,共7页
Global Traditional Chinese Medicine
基金
北京中医药大学基本科研业务费项目(2022-JYB-XJSJJ067)。
关键词
非自杀性自伤
多巴胺
疼痛奖赏
加味礞石滚痰汤
豁痰清心
non-suicidal self-injury(NSSI)
dopamine
pain reward
Jiawei Mengshi Guntan Decoction
clear phlegm and calm the heart
