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1、,中西医结合治疗脑梗死的策略,张祥建,中风脑血管病,“故生之来谓之精，两精相搏谓之神”（灵枢本神）“人始生，先成精，精成而脑髓生，骨为干，脉为营，筋为刚，肉为墙，皮肤坚而毛发长”（灵枢经脉）,“脑为元神之府”,“血者，神气也”灵枢营卫生会,血络脑血供,“人之记性皆在脑中”灵枢海论,神气脑功能,正虚血瘀浊毒内生脉道不通经络阻滞,炎症反应氧化应激兴奋氨基酸毒性线粒体功能障碍Ca2+超载,中风脑血管病,发病机制,苦参,黄连,丹参,益母草,木犀草素,水飞蓟素,姜黄,黄芩,月经不调痛经冠心病脑卒中肝炎支气管哮喘,脂溶性的丹参酮类 丹参酮 丹参酮 丹参酮水溶性的酚酸类 丹参素 丹参酸A、B、C,根皮丹而肉
2、紫,丹参,改善行为学评分,抑制脑组织炎症反应,促进神经再生,保护血脑屏障,改善脑血供,保护脑组织,减轻脑梗死面积、脑水肿,丹参酮A,Vehicle,TanA-H,NF-B,HMGB,Claudin5+IgG,HMGB,Sham Vehicle TSA-L TSA-H Sham Vehicle TSA-L TSA-H,氧化苦参碱,上调抗氧化应激因子Nrf2和HO-1,下调炎症因子TLR4/TLR2/MyD88/NF-B,TLR4,NF-B,TLR2,MyD88,Sham,Saline,OMT,抑,抑制脑组织自由基损伤,抑制神经细胞凋亡,保护缺血区线粒体,益母草碱,升高SODCAT降低MDA,Ve
3、hicle,Sham,Leo-L,Leo-H,保护缺血区线粒体超微结构,减少神经细胞凋亡,Leo-H,Leo-L,Vehicle,Sham,Bcl-2,Bax,老药新用途脑保护作用机制,黄连素,黄连素,水飞蓟素,抗炎,抗氧化,抗凋亡,保护脑组织,NF-B,pMCAO BBR-L BBR-H,减轻脑组织水肿,Sham Vehicle Silibinin-L Silibinin-H,减轻脑梗死体积,pAkt,Sham Vehicle Silibinin-L Silibinin-H,Sham pMCAO BBR-L BBR-H,pGSK3,改善行为学评分,中西医结合治疗脑梗死新策略,新策略,降低病死
4、率、致残率，提高治愈率,推动中医药的现代化发展和国际化进程,1.Tanshinone II A down-regulates HMGB1,RAGE,TLR4,NF-kappaB expression,ameliorates BBB permeability and endothelial cell function,and protects rat brains against focal ischemia.Brain Research 2010 Mar 19;1321:143-51.2.The neuroprotective effects of Tanshinone IIA are ass
5、ociated with induced nuclear translocation of TORC1 and upregulated expression of TORC1,pCREB and BDNF in the acute stage of ischemic stroke.Brain Research Bulletin,2010,82:228-233 3.Oxymatrine Downregulates TLR4,TLR2,MyD88,and NF-B and Protects Rat Brains against Focal Ischemia Mediators Inflamm.20
6、09;2009:704-706.4.Neuroprotection and underlying mechanisms of oxymatrine in cerebral ischemia of rats.Neurochemical research.2011 Apr;33(3):319-24.5.The Neuroprotection of Oxymatrine in Cerebral Ischemia/Reperfusion Is Related to Nuclear Factor Erythroid 2-Related Factor 2(Nrf2)-Mediated Antioxidan
7、t Response:Role of Nrf2 and Hemeoxygenase-1 Expression.Biological Vol.34(5):595-601,6.Leonurine protects brain injury by increased activities of UCP4,SOD,CAT and Bcl-2,decreased levels of MDA and Bax,and ameliorated ultrastructure of mitochondria in experimental stroke.Brain Research.2012 Sep 20;147
8、4:73-81.7.Neuroprotection of early and short-time applying berberine in the acute phase of cerebral ischemia:up-regulated pAkt,pGSK and pCREB,down-regulated NF-B expression,ameliorated BBB permeability.Brain Research 2012 Jun 12;1459:61-70.8.Protection by silibinin against experimental ischemic stro
9、ke:Up-regulated pAkt,pmTOR,HIF-1 and Bcl-2,down-regulated Bax,NF-B expression.Neuroscience Letters 2012 Sep 19.9.Curcumin upregulates transcription factor Nrf2,HO-1 expression and protects rat brains against focal ischemia.Brain Research,2009;1282:133-141 10.Baicalein is neuroprotective in rat MCAO
10、model:role of 12/15-lipoxygenase,mitogen-activated protein kinase and cytosolic phospholipaseA2.Pharmacology,Biochemistry and behavior,2010;96:469-475,11.Polydatin modulates inflammation by decreasing NF-B activation and oxidative stress by increasing Gli1,Ptch1,SOD1 expression and ameliorates blood
11、brain barrier permeability for its neuroprotective effect in pMCAO rat brain.Brain Research Bulletin 2012;87(1):50-5912.Inhibition of sonic hedgehog signaling aggravates brain damage associated with the down-regulation of Gli1,Ptch1 and SOD1 expression in acute ischemic stroke.Neuroscience Letters,2
12、012;506(1):1-613.Luteolin downregulates TLR4,TLR5,NF-B and p-p38MAPK expression,upregulates the p-ERK expression,and protects rat brains against focal ischemia.Brain Research 2012 Apr 11;1448:71-81.14.Protective effect of celastrol in rat cerebral ischemia model:down-regulating p-JNK,p-c-Jun and NF-
13、B.Brain Research,2012;1464:8-1315.Neuroprotective effect of early and short-time applying sophoridine in pMCAO rat brain:Down-regulated TRAF6 and up-regulated p-ERK1/2 expression,ameliorated brain infaction and edema.Brain Res Bull.2012；88：379-38416.Protective effect of luteolin in experimental ischemic stroke:upregulated SOD1,CAT,Bcl-2 and claudin-5,down-regulated MDA and Bax expression.Neurochemical research.2012 Sep;37(9):2014-24.,15,谢 谢！,
