酸枣仁汤加味对抑郁大鼠海马谷氨酸受体表达的影响  

Effect of Modified Suanzaoren Tang on Expression of Glutamate Receptor in Hippocampus of Chronic Restraibt Stress Depression Model Rat

作　　者：尚立芝[1,2] 毛梦迪 许二平 刘保光[1,2] 陈晓辉 李耀洋 汪保英[1,2] 白明 栗俞程[1,2] SHANG Li-zhi;MAO Meng-di;XU Er-ping;LIU Bao-guang;CHEN Xiao-hui;LI Yao-yang;WANG Bao-ying;BAI Ming;LI Yu-cheng(Henan University of Chinese Medicine,Zhengzhou 450046,China;Henan Key Laboratory for Modern Research of Zhongjing Compound Traditional Chinese Medicine,Zhengzhou 450046,China)

机构地区：[1]河南中医药大学,郑州450046 [2]河南省仲景方药现代研究重点实验室,郑州450046

出　　处：《中国实验方剂学杂志》2020年第23期20-26,共7页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(81973739);河南省高等学校重点科研项目(20B360011,21A630020);河南省医学科技攻关计划项目(201702203);河南省中医药科学研究专项(2019JDZX2121,2019ZY3048)。

摘　　要：目的:观察酸枣仁汤加味对慢性束缚应激抑郁大鼠海马谷氨酸受体表达的影响,探讨其基于谷氨酸受体的抗抑郁机制。方法:将60只SD大鼠随机分为正常组、模型组、酸枣仁汤加味低、中、高剂量组、氯胺酮组,每组10只。除正常组外,其余各组采用慢性束缚应激(CRS)制备大鼠抑郁模型,酸枣仁汤加味低、中、高剂量组分别灌胃酸枣仁汤加味6,12,24 g·kg-1,氯胺酮组腹腔注射氯胺酮15 mg·kg-1,正常组和模型组灌胃等体积生理盐水,1次/d,给药干预21 d。采用Morris水迷宫和新奇摄食实验评价大鼠的抑郁行为;蛋白免疫印迹法(Western blot)检测海马组织NMDAR1,NMDAR2A,NMDAR2B,GluR1,mGluR1,CaMKⅡα和CaMKⅡβ蛋白表达水平。结果:与正常组比较,模型组新奇摄食时间及逃避潜伏期显著延长(P<0.01),空间探索时间显著缩短(P<0.01);模型组大鼠海马组织NMDAR1,NMDAR2A,NMDAR2B,mGluR1和CaMKⅡβ表达水平均显著升高(P<0.01);而GluR1,CaMKⅡα水平均显著降低(P<0.01)。与模型组比较,酸枣仁汤加味中、高剂量组新奇摄食时间、逃避潜伏期显著缩短(P<0.01),空间探索时间显著延长(P<0.01);酸枣仁汤加味中、高剂量组NMDAR1,NMDAR2A,NMDAR2B,mGluR1和CaMKⅡβ蛋白表达水平均显著降低(P<0.01);而GluR1,CaMKⅡα蛋白表达显著增高(P<0.01)。结论:酸枣仁汤加味可显著改善慢性抑郁大鼠行为学,其机制可能与下调NMDAR2A,NMDAR2B,mGluR1和CaMKⅡβ表达水平,上调GluR1和CaMKⅡα表达有关。Objective:To study the effect of modified Suanzaoren Tang on the expression of excitatory amino acids receptor(EAARs) in hippocampus of rats with chronic depression, and to explore the antidepressant mechanism of modified Suanzaoren Tang based on excitatory amino acids receptor. Method: Sixty SD rats were randomly divided into normal group,model group,and low,middle and high-dose modified Suanzaoren Tang groups,and ketamine group,with 10 rats in each group. Except normal group,the depression model of rats was prepared by using chronic restraint stress(CRS). The normal group and model group were intragastrically(ig)given normal saline. the modified Suanzaoren Tang groups were intragastrically given corresponding herbal drugs 6,12,24 g·kg-1,ketamine group group were given ketamine 0.015 g·kg-1 through intraoeritoneal injection,for 21 days,once a day. Then the depressive behaviors of rats were observed by Morris water maze and novelty feeding experiment. Western blot was used to detect the levels of DAR1,NMDAR2A,NMDAR2B,GluR1,mGluR1,CaMKⅡα and CaMKⅡβ protein expression in rat hippocampus tissue. Result:Compared with normal group,the time of novel ingestion and escape latencywere prolonged significantly(P<0.01),and the time of space exploration was shortened significantly(P<0.01). The levels of NMDAR1,NMDAR2A,NMDAR2B,mGluR1 and CaMKⅡβ expression were increased significantly(P<0.01),while the levels of GluR1 and CaMKⅡ α expression were decreased significantly(P<0.01)in model group. Compared with model group,the time of novel ingestion and escape latency were shortened significantly(P<0.01),and the time of space exploration was prolonged significantly(P<0.01). The levels of NMDAR1,NMDAR2 A,NMDAR2 B,mGluR1 and CaMKⅡβ protein expression were decreased significantly(P<0.01),but the levels of GluR1 and CaMKⅡα expression were increased decreased significantly(P<0.01)in middle and high-dose modified Suanzaoren Tang groups. Conclusion: Modified Suanzaoren Tang can improve the behavior of chronic depression

关 键 词：抑郁症 酸枣仁汤 海马 谷氨酸 兴奋性氨基酸受体 

分 类 号：R2-0[医药卫生—中医学] R289