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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 被引量:6

The protective effect of salvia magnesium lithospermate B on cerebral ischemia/reperfusion injury via TGF-β pathway and the underlying mechanisms
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摘要 目的探讨丹参乙酸镁通过抑制转化生长因子-β1(transforming growth factor-β1,TGF-β1)/激活素受体激酶5(activin receptor-like kinase 5,ALK5)/SMAD2/3(drosophila mothers against decapentaplegic protein2/3)/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2 h后,再灌注24 h。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、p SMAD2/3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)、p SMAD2/3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/H 2O 2 pathway. Methods Rats were subjected to 2 h of 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 H 2O 2 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 H 2O 2 production ( P <0.01) in the rat brains, compared with I/R group. Conclusion The results suggest that lithospermate B is able to protect the brain from ischemia/reperfusion oxidative injury involved the inhibition of TGF-β1/ALK5/SMAD2/3/NOX/H 2O 2 pathway.
作者 詹舒仪 黄露露 龙思齐 周雅倩 雷文枚 娄峥 ZHAN Shuyi;HUANG Lulu;LONG Siqi;ZHOU Yaqian;LEI Wenmei;LOU Zheng(Clinical Medical College, Changsha Medical University, Changsha Hunan 410219, China;Medical Image College, Changsha Medical University, Changsha Hunan 410219, China;College of Pharmacy, Changsha Medical University, Changsha Hunan 410219, China;Hunan Jiudian Pharmaceutical Co., Ltd, Changsha Hunan 410000, China)
出处 《转化医学杂志》 2019年第1期6-10,共5页 Translational Medicine Journal
基金 湖南省教育厅一般项目(15C0161) 药学类专业校企合作人才培养示范基地(湘教通[2014]272号)
关键词 丹参乙酸镁 缺血/再灌注 转化生长因子-Β1 Salvia magnesium lithospermate B Ischemia/reperfusion injury Transforming growth factor-β1 (TGF-β1)
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