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学科主题: 基础医学
题名:
Levo-tetrahydropalmatine attenuates mouse blood-brain barrier injury induced by focal cerebral ischemia and reperfusion: Involvement of Src kinase
作者: Mao, Xiao-Wei1,2; Pan, Chun-Shui2,3,4; Huang, Ping2,3,4; Liu, Yu-Ying2,3,4; Wang, Chuan-She1,2,3,4; Yan, Li2,3,4; Hu, Bai-He2,3,4; Chang, Xin2,3,4; He, Ke2,3,4; Mu, Huan-Na2,3,4; Li, Quan2,3,4; Sun, Kai2,3,4; Fan, Jing-Yu2,3,4; Han, Jing-Yan1,2,3,4
刊名: SCIENTIFIC REPORTS
发表日期: 2015-06-10
DOI: 10.1038/srep11155
卷: 5
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Multidisciplinary Sciences
研究领域[WOS]: Science & Technology - Other Topics
关键词[WOS]: MATRIX METALLOPROTEINASES ; TYROSINE PHOSPHORYLATION ; STROKE ; DISRUPTION ; INHIBITION ; ACTIVATION ; ADDICTION ; MECHANISM ; MEMBRANE
英文摘要:

The restoration of blood flow following thrombolytic therapy causes ischemia and reperfusion (I/R) injury leading to blood-brain barrier (BBB) disruption and subsequent brain edema in patients of ischemic stroke. Levo-tetrahydropalmatine (l-THP) occurs in Corydalis genus and some other plants. However, whether l-THP exerts protective role on BBB disrpution following cerebral I/R remains unclear. Male C57BL/6N mice (23 to 28 g) were subjected to 90 min middle cerebral artery occlusion, followed by reperfusion for 24 h. l-THP (10, 20, 40 mg/kg) was administrated by gavage 60 min before ischemia. We found I/R evoked Evans blue extravasation, albumin leakage, brain water content increase, cerebral blood flow decrease, cerebral infarction and neurological deficits, all of which were attenuated by l-THP treatment. Meanwhile, l-THP inhibited tight junction (TJ) proteins down-expression, Src kinase phosphorylation, matrix metalloproteinases-2/9 (MMP-2/9) and caveolin-1 activation. In addition, surface plasmon resonance revealed binding of l-THP to Src kinase with high affinity. Then we found Src kinase inhibitor PP2 could attenuate Evans blue dye extravasation and inhibit the caveolin-1, MMP-9 activation, occludin down-expression after I/R, respectively. In conclusion, l-THP attenuated BBB injury and brain edema, which were correlated with inhibiting the Src kinase phosphorylation.

语种: 英语
所属项目编号: 2013ZX09402202
项目资助者: Production of New Medicine Program of Ministry of Science and Technology of China
WOS记录号: WOS:000356086100001
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/65802
Appears in Collections:基础医学院_期刊论文

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作者单位: 1.Peking Univ, Sch Basic Med Sci, Dept Integrat Chinese & Western Med, Beijing 100871, Peoples R China
2.State Adm Tradit Chinese Med China, Key Lab Microcirculat, Beijing, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Tasly Microcirculat Res Ctr, Beijing 100871, Peoples R China
4.State Adm Tradit Chinese Med China, Key Lab Stasis & Phlegm, Beijing, Peoples R China

Recommended Citation:
Mao, Xiao-Wei,Pan, Chun-Shui,Huang, Ping,et al. Levo-tetrahydropalmatine attenuates mouse blood-brain barrier injury induced by focal cerebral ischemia and reperfusion: Involvement of Src kinase[J]. SCIENTIFIC REPORTS,2015,5.
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