基于突触相关蛋白探讨清热利胆解毒方干预高铜诱导大鼠抑郁样行为的作用机制  

Exploring the Mechanism of Qingre Lidan Jiedu Recipe interferes with high copper-induced depression-like behavior in rats based on synapse-associated protein

作　　者：孙正哲 方向[1,2] 金珊[1,2] 杨文明[2] 王山 范金伟 SUN Zhengzhe;FANG Xiang;JIN Shan(Anhui University of Chinese Medicine,Hefei Anhui 230038,China;The First Affiliated Hospital of Anhui University of Chinese Medicine,Hefei Anhui 230031,China)

机构地区：[1]安徽中医药大学,安徽合肥230038 [2]安徽中医药大学第一附属医院,安徽合肥230031

出　　处：《四川中医》2023年第8期65-70,共6页Journal of Sichuan of Traditional Chinese Medicine

基　　金：国家自然科学基金面上项目(编号:81973825);安徽省高校自然科学研究重点项目(编号:KJ2019A0457);安徽省自然科学基金面上项目(编号:2008085MH264、2208085MH271);安徽中医药大学科研基金项目(编号:2021yfylc10)。

摘　　要：目的:观察清热利胆解毒方对高铜诱导大鼠抑郁样行为的影响,并基于生长相关蛋白43(growth associated protein,GAP-43)、微管相关蛋白2(microtubule associated protein-2,MAP-2)探讨其治疗机制。方法:75只SD雄性大鼠随机选取10只作为空白(NG)组,其余大鼠予以1g/kg的高铜饲料及0.185%硫酸铜去离子水喂养制备铜负荷大鼠模型,12周后通过行为学测定(旷场试验、悬尾实验)筛选出具有抑郁样行为的铜负荷大鼠40只,随机分为模型(MG)组、清热利胆解毒方(TCM)组、青霉胺(PCA)组和清热利胆解毒方加青霉胺(TCM+PCA)组,每组10只;第13周起各组大鼠开始灌胃给药,连续治疗6周,给药结束前进行5天的旷场实验、悬尾实验检测大鼠抑郁样行为的变化情况。采用Western-blot技术检测海马区突触相关蛋白GAP-43、MAP-2表达水平。结果:旷场实验中模型组大鼠的直立次数、跨格次数较空白组显著减少(P<0.01),中药组较模型组明显增多(P<0.01),中药组较西药组无明显差异(P>0.05);悬尾实验中模型组大鼠的悬尾不动时间较空白组显著延长(P<0.01),中药组较模型组明显降低(P<0.01),中药组较西药组无明显差异(P>0.05)。模型组大鼠较空白组大鼠海马区GAP-43、MAP-2的表达均明显减少(P<0.05),中药组较模型组GAP-43、MAP-2的表达均明显增加(P<0.05),中药组较西药组无明显差异(P>0.05)。结论:清热利胆解毒方可能通过调节海马区GAP-43及MAP-2的表达发挥着改善高铜诱导大鼠抑郁样行为的作用。Objective:To observe the effect of Qingre Lidan Jiedu Recipe on depression-like behavior in rats induced by high copper levels,and explore its therapeutic mechanism based on growth-associated protein 43(GAP-43)and microtubuleassociated protein 2(MAP-2).Methods:10 of 75 male SD rats were randomly selected as the blank(NG)group,and the remaining rats were fed with 1g/kg of high copper diet and 0.185%copper sulfate deionized water to prepare a copper-loaded rat model.After 12 weeks,40 copper-loaded rats with depression-like behaviour were selected by behavioral tests(open field test,tail suspension test)and randomly divided into model(MG)group,TCM group,penicillamine(PCA)group and TCM+PCA group,with 10 rats in each group;The rats were treated by gavage for consecutive 6 weeks from the 13th week,and they were tested for changes in depression-like behavior by the open-field and hanging-tail tests for 5 days before the end of the administration.Western-blot technique was used to detect the expression levels of synaptic-associated proteins GAP-43 and MAP-2 in the hippocampus.Results:In the open-field test,the number of upright and cross-frame rats in the model group was significantly reduced compared with the blank group(P<0.01),and the number of times in the Chinese medicine group was significantly increased compared with the model group(P<0.01),while there was no significant difference between the Chinese medicine group and the western medicine group(P>0.05);In the tail suspension test,the immobility time of the rats in the model group was significantly longer than that of the blank group(P<0.01),and that of the Chinese medicine group was significantly lower than that of the model group(P<0.01),but there was no significant difference between the Chinese medicine group and the western medicine group(P>0.05);The expression of GAP-43 and MAP-2 in the hippocampus of rats in the model group was significantly reduced compared with that in the blank group(P<0.05),and the expression of GAP-43 and MAP-2 in the Chinese medicine

关 键 词：清热利胆解毒方 肝豆状核变性 大鼠 神经行为功能 抑郁样行为 GAP-43 MAP-2 

分 类 号：R285.5[医药卫生—中药学]