当归补血汤及其主要活性成分阿魏酸对糖尿病抑郁症模型大鼠的影响及机制研究  

Effects of Danggui Buxue Decoction and Its Main Active Ingredient Ferulic Acid on CUMS Model GK Rats

作　　者：王文恺 张蔚 孙悦 钟琪 薛梅[1,4] WANG Wenkai;ZHANG Wei;SUN Yue;ZHONG Qi;XUE Mei(College of Chinese Medicine of Nanjing University of Chinese Medicine,Nanjing 210023 Jiangsu,China;Zhenjiang Mental Health Center,Zhenjiang 212000 Jiangsu,China;First Clinical College,Nanjing University of Chinese Medicine,Nanjing 210023 Jiangsu,China;Institute of Common Disease and Depression,Nanjing University of Chinese Medicine,Nanjing 210023 Jiangsu,China)

机构地区：[1]南京中医药大学中医学院,江苏南京210023 [2]镇江市精神卫生中心,江苏镇江212000 [3]南京中医药大学第一临床医学院,江苏南京210023 [4]南京中医药大学共病郁证研究所,江苏南京210023

出　　处：《中药新药与临床药理》2020年第6期649-654,共6页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：江苏省中医药局资助项目(YB201802);江苏省大学生创新创业训练计划项目(201910315056Y)。

摘　　要：目的探讨当归补血汤及其主要活性成分阿魏酸对糖尿病抑郁症(Diabetes mellitus with depression,DD)模型大鼠的影响及机制。方法将32只雄性自发性2型糖尿病(Goto-Kakizaki,GK)大鼠随机分为模型组、氟西汀组(2.20 mg·kg^-1)、当归补血汤组(4.0 g·kg^-1)和阿魏酸组(1.36 mg·kg^-1),每组8只,另取8只普通Wistar大鼠作为正常对照组。采用慢性温和不可预知性应激抑郁(Chronic unpredictable mild stress,CUMS)模型复制方法造模,同时按上述剂量灌胃给药(10 mL·kg^-1),每日1次,连续4周。全程监测动物体质量及随机血糖;末次给药后,采用悬尾试验、强迫游泳和旷场实验观察动物行为学变化;采用ELISA法测定大鼠血清和海马组织中脑源性神经营养因子(BDNF)、环磷腺苷效应元件结合蛋白(CREB)、酪氨酸激酶受体B(TrkB)的含量;采用HE染色法进行大鼠海马组织病理形态学观察。结果与正常对照组比较,模型组大鼠体质量逐渐下降,血糖值始终明显升高(P <0.01);大鼠悬尾和强迫游泳的不动时间明显增加,而在旷场的自主运动总距离明显减少(P <0.001);血清BDNF及海马组织CREB、BDNF、TrkB的含量均明显降低(P <0.001)。与模型组比较,各给药组大鼠体质量逐渐增加,在给药2周后开始随机血糖值均明显下降(P <0.05,P <0.01);悬尾和强迫游泳不动时间明显缩短,自主运动距离明显增加(P <0.01,P <0.05);血清BDNF及海马组织CREB、BDNF、TrkB含量均明显上升(P <0.05,P <0.01)。结论当归补血汤及其主要活性成分阿魏酸能够显著改善糖尿病抑郁模型大鼠的抑郁样行为,保护海马神经元,其作用机制可能与CREB/BDNE/TrkB信号通路有关。Objective To observe the intervention effect of Danggui Buxue decoction(DBD) and its main active ingredient ferulic acid(FA)on depressive Goto-Kakizaki(GK)rats induced by chronic unpredictable mild stress,and to explore its mechanism. Methods Thirty-two male GK rats were divided into model group,fluoxetine group(2.20 mg·kg^-1),Danggui Buxue decoction group(4.0 g·kg^-1)and ferulic acid group(1.36 mg·kg^-1);8 common Wistar rats were assigned to be a normal control group. Modeling was performed using the Chronic unpredictable mild stress(CUMS)model,and the drugs were administered as described once daily for 4 weeks. Animals’ body weight and random blood glucose were monitored throughout. After the last administration,the behavioral changes of the animals were observed by tail suspension test, forced swimming test and open field test. The contents of brainderived neurotrophic factor(BDNF), cAMP-response element binding protein(CREB) and tropomyosin receptor kinase B(TrkB) in rats’ serum and hippocampus were determined by ELISA;HE staining was used to observe the hippocampal morphology of rats. Results Compared with the normal control group,the body weight of the model group decreased gradually,level of the random blood glucose was higher(P < 0.01);the movement distance of the model group was significantly decreased in the open field(P < 0.001),the immobility time of the tail suspension and forced swimming were significantly increased(P < 0.001);the expression levels of serum BDNF and hippocampal CREB,BDNF and TrkB were significantly reduced(P < 0.01),and the microscopic morphology of hippocampus cells was changed. Compared with the model group, the body weights of all treated groups were gradually increased,and the levels of random blood glucose were significantly decreased(P < 0.05,P < 0.01);the distance of movement in the open field was significantly increased(P < 0.01 or P < 0.05). The immobility time of tail and forced swimming were significantly reduced(P < 0.01,P < 0.05),and the expression levels of seru

关 键 词：当归补血汤 阿魏酸 糖尿病抑郁症 大鼠 脑源性神经营养因子 环磷腺苷效应元件结合蛋白 酪氨酸激酶受体B 

分 类 号：R285.5[医药卫生—中药学]