黄芩苷改善慢性脑低灌注大鼠认知障碍的作用及机制研究  

Effect of baicalin on cognitive impairment in rats with chronic cerebral hypoperfusion and its mechanism

作　　者：陈景 杨磊 左亚杰 张琴 彭词艳[2] CHEN Jing;YANG Lei;ZUO Ya-jie;ZHANG Qin;PENG Ci-yan(Department of Pharmaceutical Preparation,the First Hospital of Hunan University of Chinese Medicine,Changsha 410007;Department of Pharmacy,The Second Xiangya Hospital of Central South University,Changsha 410011)

机构地区：[1]湖南省中医药大学第一附属医院制剂部,长沙410007 [2]中南大学湘雅二医院药学部,长沙410011

出　　处：《中南药学》2021年第7期1333-1338,共6页Central South Pharmacy

摘　　要：目的观察不同剂量黄芩苷(50、100、200 mg·kg^(-1))对慢性脑低灌注(CCH)所致大鼠认知障碍的保护作用,并进一步探讨其作用机制。方法大鼠双侧颈总动脉结扎建立CCH模型。采用水迷宫实验评价大鼠的空间学习记忆;新事物认知实验评价大鼠的非空间学习记忆;在体场电位记录长时程增强(LTP)评价大鼠海马CA1区突触可塑性的变化;Western Blot检测大鼠海马CA1区神经元核(NeuN)、突触素(SYP)、磷酸化核因子E2相关因子2(p-Nrf2)以及血红素加氧酶-1(HO-1)的表达;试剂盒检测氧化应激指标谷胱甘肽过氧化物酶(GSH-Px)、超氧化物歧化酶(SOD)、丙二醛(MDA)的变化。结果CCH能导致大鼠出现显著的空间及非空间学习记忆损伤,并伴随海马CA1区LTP抑制及NeuN和SYP的表达下调。给予100、200 mg·kg^(-1)黄芩苷能显著改善CCH大鼠的学习记忆损伤及LTP抑制;并且100 mg·kg^(-1)黄芩苷可逆转CCH大鼠海马CA1区NeuN和SYP的表达下调。进一步探讨机制发现黄芩苷可显著上调CCH大鼠海马CA1区GSHPx和SOD活性,下调MDA含量,并显著上调p-Nrf2及HO-1的蛋白表达。结论黄芩苷能改善CCH所致的认知障碍,其作用可能与激活Nrf2/HO-1信号通路从而抑制氧化应激损伤有关。Objective To observe the protective effect of baicalin(50,100,and 200 mg·kg^(-1))on cognitive impairment caused by chronic cerebral hypoperfusion(CCH),and explore its mechanism.Methods The CCH model of rats was established by ligation of bilateral common carotid artery.Water maze experiment was used to evaluate the spatial learning and memory of rats.Non-spatial learning and memory of rats were evaluated by novel object recognition test.Long term enhancement(LTP)was recorded to evaluate the changes of synaptic plasticity in the hippocampal CA1 region of the rats.The expression of NeuN,SYP,p-Nrf2 and HO-1 was detected by Western Blot.The change of GSH-Px,SOD and MDA was detected by test kit.Results CCH caused significant spatial and non-spatial learning and memory impairment in rats,accompanied by inhibition of LTP and downregulation of NeuN and SYP expression in the hippocampal CA1.Middle and high dose of baicalin(100 and 200 mg·kg^(-1))could significantly improve the learning and memory impairment and reverse the inhibition of LTP in rats with CCH.Moreover,100 mg·kg^(-1) baicalin improved the down-regulation of NeuN and SYP expression in the hippocampal CA1.Furthermore,baicalin could increased the GSH-Px and SOD activity,reduced the MDA content,and markedly increased the p-Nrf2 and HO-1 expression in the hippocampal CA1 of rats with CCH.Conclusion Baicalin can alleviate the cognitive impairment caused by CCH,with its mechanism via activating Nrf2/HO-1 signaling pathways to inhibit the oxidative stress injury.

关 键 词：黄芩苷 慢性脑低灌注 认知障碍 氧化应激 

分 类 号：R285.5[医药卫生—中药学]