川芎注射液通过cAMP-CREB-BDNF通路改善卒中后抑郁大鼠神经功能  

Chuanxiong injection improves neurological function of post-stroke depression rats through cAMP-CREB-BDNF pathway

作　　者：喻斌[1] 阮鸣[1,2] 许立 李宏轶[3] YU Bin;RUAN Ming;XU Li;LI Hong-yi(Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica,Nanjing University of Chinese Medicine,Nanjing 210023,China;School of Food Technology,Nanjing Xiaozhuang University,Nanjing 211117,China;Jiangsu Nanxing Pharmaceutical Co.,Ltd,Nanjing 210046,China)

机构地区：[1]南京中医药大学江苏省中药药效与安全性评价重点实验室,江苏南京210023 [2]南京晓庄学院食品科学学院,江苏南京211117 [3]江苏南星药业有限责任公司,江苏南京210046

出　　处：《中国药理学通报》2022年第8期1246-1251,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No.81973726)。

摘　　要：目的探讨川芎注射液对卒中后抑郁(post-stroke depression,PSD)神经功能的保护作用及对海马cAMP-CREB-BDNF通路的影响。方法大鼠随机分为假手术组、模型组、川芎注射液低剂量组(0.1 g·kg^(-1))和高剂量组(0.2 g·kg^(-1)),采用中动脉阻断联合慢性应激刺激构建PSD模型。给药后通过糖水消耗、开场实验和Morris水迷宫实验观察动物行为学,通过尼氏染色和Neun免疫荧光检测海马CA1区神经细胞功能和状态,利用Western blot观察海马cAMP-CREB-BDNF通路蛋白的表达。结果川芎注射液低、高剂量组均明显增加PSD大鼠糖水饮用量、大鼠水平和垂直运动,减少游泳总路程和近站台区路程,改善CA1区尼氏体的数量和形态,增加海马组织cAMP、p-CREB的表达。此外,高剂量组还能缩短登台潜伏期,减少近/远站台区路程比,增加Neun和BDNF的表达。结论川芎注射液可通过上调cAMP-CREB-BDNF通路,改善PSD大鼠行为学和神经功能,保护海马CA1区神经细胞,缓解抑郁大鼠认知功能的受损。Aim To explore the neuroprotection of Chuanxiong injection on post-stroke depression(PSD)and its effect on cAMP-p-CREB-BDNF pathway in hippocampus.Methods Rats were randomly divided into four groups of sham,model,low-dose(0.1 g·kg^(-1))of Chuanxiong injection and high-dose(0.2 g·kg^(-1))of it.The PSD model was established by middle cerebral artery occlusion(MCAO)combined with chronic stress stimulation.After the treatment,the behaviors of rats were observed by the tests of sugar consumption,open-field and Morris water maze.The function and status of neurons in hippocampus CA1 area were detected by Nissl staining and Neun immunofluorescence.The expressions of cAMP-p-CREB-BDNF pathway proteins in hippocampus were observed by Western blot.Results Both Chuanxiong injection groups of low-dose and high-dose significantly increased consumption of sugar water,horizontal and vertical movement scores,decreased total route distance and route near the plat,elevated the number of Nissl body in CA1 area,restored the morphology of Nissl body,and enhanced the expressions of cAMP and p-CREB in hippocampus.Additionally,the high dose group shortened swimming duration,reduced distance ratio of near plat to far from plat,and increased the expressions of Neun and BDNF.Conclusions Chuanxiong injection has the potential of improving the behavior and neurological function of PSD rats via up-regulating cAMP-CREB-BDNF pathway,protecting the neurons in hippocampal CA1 area,and ultimately alleviating the cognitive deficiency of PSD rats.

关 键 词：川芎注射液 卒中后抑郁 行为学 神经功能 cAMP-CREB-BDNF通路 神经元保护 

分 类 号：R-332[医药卫生] R282.71R322.81R342.4R743.3R749.42