丹参乙酸镁通过抑制TGF-β途径减轻脑缺血/再灌注损伤的保护作用及机制

The prot ecit ve effect of savl iamag neisum lit hospermat e B on cerebral ischemia/rpeerfusion Injury via TGF-βpathway and the und erl ynig mechani sms

目的:探讨丹参乙酸镁通过抑制转化生长因子-β1(transformationgrowthfactor-β1,TGF-β1)/激活素受体激酶5(activin receptor-like kinase 5,ALK5)/SMAD2/3(drosophila mothers against decapentaplegic protein 2/3)/NADPH氧化酶(NADPH oxidase,NOX)/H2O2途径产生对大鼠脑缺血/再灌注损伤的保护作用。方法:构建大鼠线栓法脑缺血/再灌注模型,使大鼠脑缺血2h后,再灌注24h。实验动物随机平分为假手术组(sham组),脑缺血/再灌注组(I/R组),脑缺血/再灌注+丹参乙酸镁组(I/R+MLB组)和脑缺血/再灌注+溶媒组(I/R+vehicle组)4组,分别检测sham组,I/R组,I/R+MLB组以及I/R+vehide组动物死亡率,神经学评分,脑梗死体积,脑内TGF-β1含量,ALK5 mRNA及蛋白含量,pSMAD2/3蛋白含量,NOX活性及H2O2水平。结果:与I/R组比较,I/R+MLB组大鼠脑组织梗死体积明显缩小(P<0.01),TGF-β1含量(P<0.05)、pSMAD2/3蛋白含量(P<0.01),NOX活性(P<0.01)和H2O2水平(P<0.01)均降低。结论:丹参乙酸镁具有抗脑缺血再/灌注损伤的作用,其机制与抑制TGF-β1/ALK5/SMAD2/3/NOX/H2O2通路有关。

Objective:This study aims to investigate whether salvia magnesium lithospermate B is able to protect the rat brain from ischemia/reperfusion injury via inhibition of transforming growth Factor-β1(TGF-β1)activin receptor-like kinase 5(ALK5)/drosophila mothers against decapentaplegic protein 2/3(SMAD2/3)/nicotinamide adenine dinucleotide phosphate-oxidase NOX/H2O2 pathway.Methods:Rats emerges to 2 h cerebral ischemia and 24 h of reperfusion to establish an ischemia/reperfusion injury model.The mortality rate,neurological score,cerebral infarct volume on animals,TGF-β1 content,ALK5 mRNA and protein content,pSMAD2/3 protein content,nicotinamide adenine dinucleotide phosphate-oxidase NOX activity,and H2O2 content in brain were examined on Sham group,I/R group,I/R+MLB group and I/R+vehicle group.Results:Administration of salvia magnesium lithospermate B reduced cerebral infarct volume(P<0.01),decreased TGF-β1 conTent(P<0.05),pSMAD2/3 protein content(P<0.01),NOX activity(P<0.01)and H2O2 produc Tion(P<0.01)in the rat brain,scompared with I/R group.Cnoclusion:The results suggest that Lithospermate B is able to protect the brain from ischemia/reperfusion oxidative injury involved the in Ihibition of TGF-β1/ALK5/SMAD2/3/NOX/H2O2 pathway..