三七总皂苷治疗缺血性脑卒中的神经保护机制  

The neuroprotection molecular basis and mechanism of Panax Notoginseng saponins in the treatment of ischemic stroke

作　　者：王萍 闫东明 黄茜 郑晓琼 任超 杨兆祥 张建文 WANG Ping;YAN Dong-ming;HUANG Xi;ZHENG Xiao-qiong;REN Chao;YANG Zhao-xiang;ZHANG Jian-wen(Biology Department of Institute of Drug Discovery and Development,KPC Pharmaceutical Inc,Kunming 650100,China)

机构地区：[1]昆药集团股份有限公司药物研发平台生物学部,云南昆明650100

出　　处：《中国药理学通报》2018年第12期1750-1755,共6页Chinese Pharmacological Bulletin

基　　金：云南省科技厅海外高层次科技创新人才引进计划项目(No 2013HA018)

摘　　要：目的从抗炎角度探索三七总皂苷(PNS)与阿替普酶(r-tPA)联用对缺血性脑卒中的治疗作用。方法在线栓法致大鼠局灶性脑缺血模型中,考察PNS在不同时间点给药的脑保护作用;以凝血酶致大鼠局灶性脑缺血模型,考察PNS与阿替普酶联用的治疗作用;流式细胞术检测PNS对线栓法致小鼠局灶性脑缺血梗死侧大脑巨噬细胞聚集的影响;用PNS处理LPS诱导的炎症细胞模型,ELISA法检测炎性因子的表达。结果于缺血/再灌注前或再灌注后给予PNS,均能明显降低模型鼠的行为学评分及脑梗死百分率,且r-tPA联合PNS(40 mg·kg^(-1))对模型鼠具有更优的治疗效果。同时,给予PNS治疗的小鼠梗死侧大脑巨噬细胞的数量呈下降趋势。100 mg·L^(-1)的PNS预处理能明显抑制巨噬细胞和小胶质细胞TNF-α和IL-6的表达。结论溶栓联合PNS治疗脑卒中动物模型疗效明显,提示血管再通时进行抗炎症反应管理可以减轻再灌注脑损伤和增强神经保护作用。Aim To explore the molecular basis of neuroprotection of Panax Notoginseng saponins （PNS） combined with alteplase （r-tPA） in treatment of ischemic stroke. Methods The middle cerebral artery occlusion （MCAO） rat model with the filament was used to examine the cerebral protective effect of PNS that administered at different time points. And the fibrin-rich thrombotic focal cerebral ischemic rat model was used to investigate the combination therapy of PNS and r-tPA. The impact of PNS on cerebral infarction and macrophage accumulation in MCAO mouse model were assessed by flow cytometry. The inhibitory action of PNS toward pro-inflammatory cytokine expressions in cultural macrophage and microglia challenged with LPS were evaluated by using ELISA. Results The administration of PNS alone before or after reperfusion in MCAO rats significantly reduced the size of cerebral infarction and improved neurological outcomes in model rats. The combination treatment of r-tPA plus PNS （40 mg·kg^ -1 ） showed much better therapeutic efficacy in the fibrin-rich thrombotic focal cerebral ischemic rat model. There was a significant reduction in infiltration of macrophages in the infracted area of brain of MCAO mice pre-treated with PNS. Furthermore,it was proved that the expressions of pro-inflammatory cytokines （TNF-α and IL-6） was significantly down-regulated by pre-treatment with PNS in LPS-induced macrophages and microglia models. Conclusion The combination therapy of thrombolysis plus PNS showeds a much profound therapeutic effects on the stroke animal models,which suggesteds that anti-inflammatory management could reduce reperfusion brain damage and boost neuroprotection during recanalization.

关 键 词：阿替普酶 三七总皂苷 脑缺血性损伤 神经保护 损伤相关分子模式 炎性因子 

分 类 号：R-332[医药卫生] R284.1