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salvianolic acid A attenuates ischemia reperfusion induced rat brain damage by protecting the blood brain barrier through MMP-9 inhibition and anti-inflammation

引用

Chinese Journal of Natural Medicines 2018年第3期16卷 184-193页

作者： ZHANG Wen SONG Jun-Ke ZHANG Xue ZHOU Qi-Meng HE Guo-Rong XU Xiao-Na Yan Rong ZHOU Wen-Xia DU Guan-Hua Beijing Key Laboratory of Drug Target Identification and Drug Screening Institute of Materia Medica Chinese Academy of Medical Sciences & Peking Union Medical College Department of Neuroimmunopharmacology Beijing Institute of Pharmacology and Toxicology State Key Laboratory of Toxicology and Medical Countermeasures

salvianolic acid A(SAA) is a water-soluble component from the root of Salvia Miltiorrhiza Bge, a traditional Chinese medicine, which has been used for the treatment of cerebrovascular diseases for centuries. The present study aimed to determine the brain protective effects of SAA against cerebral ischemia reperfusion injury in rats, and to figure out whether SAA could protect the blood brain barrier(BBB) through matrix metallopeptidase 9(MMP-9) inhibition. A focal cerebral ischemia reperfusion model was induced by middle cerebral artery occlusion(MCAO) for 1.5-h followed by 24-h reperfusion. SAA was administered intravenously at doses of 5, 10, and 20 mg?kg–1. SAA significantly reduced the infarct volumes and neurological deficit scores. Immunohistochemical analyses showed that SAA treatments could also improve the morphology of neurons in hippocampus CA1 and CA3 regions and increase the number of neurons. Western blotting analyses showed that SAA downregulated the levels of MMP-9 and upregulated the levels of tissue inhibitor of metalloproteinase 1(TIMP-1) to attenuate BBB injury. SAA treatment significantly prevented MMP-9-induced degradation of ZO-1, claudin-5 and occludin proteins. SAA also prevented cerebral NF-κB p65 activation and reduced inflammation response. Our results suggested that SAA could be a promising agent to attenuate cerebral ischemia reperfusion injury through MMP-9 inhibition and anti-inflammation activities.

关键词： Salvianolic 酸 A 局部缺血 MCAO 血大脑障碍 NF-B MMP-9

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