Clematichinenoside protects blood brain barrier against ischemic stroke superimposed on systemic inflammatory challenges through up-regulating A20

被引：38
作者：
Han, Dan [1 ]
Fang, Weirong [1 ]
Zhang, Rui [1 ]
Wei, Jie [1 ]
Kodithuwakku, Nandani Darshika [1 ]
Sha, Lan [1 ]
Ma, Wenhuan [1 ]
Liu, Lifang [2 ,3 ]
Li, Fengwen [4 ]
Li, Yunman [1 ]
机构：
[1] China Pharmaceut Univ, Dept Physiol, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China
[2] China Pharmaceut Univ, Dept Pharmacognosy, Nanjing 210009, Jiangsu, Peoples R China
[3] China Pharmaceut Univ, Key Lab Modern Chinese Med, Minist Educ, Nanjing 210009, Jiangsu, Peoples R China
[4] China Pharmaceut Univ, Dept Tradit Chinese Pharm, Nanjing 210009, Jiangsu, Peoples R China
来源：
BRAIN BEHAVIOR AND IMMUNITY | 2016年 / 51卷
基金：
中国国家自然科学基金;
关键词：
Clematichinenoside; Blood brain barrier; Systemic inflammation; Ischemic stroke; Zinc finger protein A20; NF-kappa B; NF-KAPPA-B; TUMOR-NECROSIS-FACTOR; CEREBRAL-ARTERY OCCLUSION; IN-VIVO; SODIUM-SALICYLATE; ENDOTHELIAL-CELLS; INDUCED ARTHRITIS; INFECTION; NEUROPROTECTION; ACTIVATION;
D O I：
10.1016/j.bbi.2015.07.025
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
Suppression of excessive inflammation can ameliorate blood brain barrier (BBB) injury, which shows therapeutic potential for clinical treatment of brain injury induced by stroke superimposed on systemic inflammatory diseases. In this study, we investigated whether and how clematichinenoside (AR), an anti-inflammatory triterpene saponin, protects brain injury from stroke superimposed on systemic inflammation. Lipopolysaccharide (LPS) was intraperitoneally injected immediately after middle cerebral artery occlusion (MCAO) in rats. Rat microvessel endothelial cells (rBMECs) were exposed to hypoxia/reoxygenation (H/R) coexisting with LPS. The results revealed that AR suppressed the excessive inflammation, restored BBB dysfunction, alleviated brain edema, decreased neutrophil infiltration, lessened neurological dysfunction, and decreased infarct rate. Further study demonstrated that the expression of nucleus nuclear factor kappa B (NF-kappa B), inducible nitric oxide synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor-alpha (TNF-alpha) and interlukin-1 beta (IL-1 beta) were suppressed by AR via zinc finger protein A20. Besides, AR increased in vitro BBB integrity through A20. In conclusion, AR alleviated cerebral inflammatory injury through A20-NF-kappa B signal pathway, offering an alternative medication for stroke associated with systemic inflammatory diseases. (C) 2015 Elsevier Inc. All rights reserved.
引用
收藏
页码：56 / 69
页数：14
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