摘要
目的探讨丹灯通脑胶囊对脑缺血再灌注损伤大鼠的保护作用及可能作用机制,对丹灯通脑胶囊临床药效再评价。方法采用线栓法复制大脑中动脉栓塞(middle cerebral artery occlusion,MCAO)模型,缺血2 h后拔出线栓造成缺血再灌注损伤(ischemia reperfusion injury,I/R)。TTC染色法观察丹灯通脑胶囊对脑梗死体积的影响。激光多普勒血流仪(laser doppler flowmetery,LDF)测定缺血再灌注大鼠局部脑血流量;采用苏木素伊红(hematoxylin and eosin,HE)染色、透射电镜(transmission electron microscopy,TEM)观察大鼠海马神经元损伤;微透析系统检测脑缺血后氨基酸含量变化;流式分析预防治疗脑内海马钙离子含量。结果结果显示,与模型组相比,丹灯通脑胶囊组大鼠7、14 d脑血流量回升且脑梗死体积下降;海马CA1区神经元损伤明显减轻;脑内兴奋性氨基酸含量和海马内钙离子含量降低。结论提示丹灯通脑胶囊有明显预防和治疗大鼠脑缺血再灌注损伤,该保护作用可能与抑制兴奋性氨基酸释放及减少胞内钙离子有关。
OBJECTIVE To observe the protective effects of Dandeng Tongnao capsule(DDTN)on cerebral ischemia reperfusion injury in rat and explore its mechanism so as to reevaluation the clinical efficacy of DDTN.METHODS Middle cerebral artery occlusion(MCAO)model in rats was established using filament method and reperfusion was processed with filament removed 2 h later.Therefore,the MCAO models were established to observe the effect of DDTN-L group(0.21 g·kg^-1)and DDTN-H group(0.84 g·kg^-1)on infract volume via TTC staining.Regional cerebral blood flow(rCBF)of corpus striatum of the side of cerebral infraction was measured by using laser doppler flow(LDF).Pathological changes of neuron in hippocampuses were observed via hematoxylin and eosin(HE)staining and transmission electron microscopy(TEM).The changes of amino acid in cerebral ischemia were detected by microdialysis system.The level of Ca^2+ was evaluated by flow cytometer(FCM).RESULTS The results showed that the cerebral blood flow increased and infract volume reduced at 7,14 d in DDTN group.Analysis of HE staining and TEM scan suggested that DDTN(0.21,0.84 g·kg^-1)remarkably alleviated neuronal injury of hippocampal CA1 area during I/R.The contents of Ca^2+ and excitatory amino acids were significantly decreased in DDTN group.CONCLUSION DDTN could prevent cerebral injury of MCAO rats via decreasing the intracellular Ca2+concentration,and inhibiting the release of excitatory amino acids.
作者
李丹
吴思鹏
侯金才
赵丽
汪宁
LI Dan;WU Si-peng;HOU Jin-cai;ZHAO Li;WANG Ning(Jing-Jin-Ji Joint Innovation Pharmaceutical(Beijing)Co.,Ltd.,Beijing 100083,China;Key Laboratory of Chinese Medicinal Formula of Anhui Province,Anhui University of Chinese Medicine,Hefei 230012,China;Institute for Pharmacodynamics and Safety Evaluation of Chinese Medicine,Anhui Academy of Chinese Medicine,Hefei 230012,China)
出处
《中国药学杂志》
CAS
CSCD
北大核心
2019年第20期1670-1676,共7页
Chinese Pharmaceutical Journal
基金
北京市科技计划课题资助(Z161100002616024)
关键词
丹灯通脑胶囊
脑缺血
微透析
局部血流量
激光多普勒血流仪
Dandeng-Tongnao granule
cerebral ischemia
microdialysis
regional cerebral blood flow
laser doppler flow
