title: Levo-tetrahydropalmatine attenuates mouse blood-brain barrier injury induced by focal cerebral ischemia and reperfusion: Involvement of Src kinase.
abstract: 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 disruption 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.
authors.affiliation: 1] Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China [2] Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of China, Beijing, China.
authors.forename: Xiao-Wei
authors.initials: XW
authors.lastname: Mao
authors.affiliation: 1] Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of China, Beijing, China [2] Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China [3] Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of China, Beijing, China.
authors.forename: Chun-Shui
authors.initials: CS
authors.lastname: Pan
authors.affiliation: 1] Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of China, Beijing, China [2] Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China [3] Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of China, Beijing, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Huang
authors.affiliation: 1] Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of China, Beijing, China [2] Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China [3] Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of China, Beijing, China.
authors.forename: Yu-Ying
authors.initials: YY
authors.lastname: Liu
authors.affiliation: 1] Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China [2] Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of China, Beijing, China [3] Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China [4] Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of China, Beijing, China.
authors.forename: Chuan-She
authors.initials: CS
authors.lastname: Wang
authors.affiliation: 1] Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of China, Beijing, China [2] Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China [3] Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of China, Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yan
authors.affiliation: 1] Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of China, Beijing, China [2] Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China [3] Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of China, Beijing, China.
authors.forename: Bai-He
authors.initials: BH
authors.lastname: Hu
authors.affiliation: 1] Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of China, Beijing, China [2] Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China [3] Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of China, Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Chang
authors.affiliation: 1] Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of China, Beijing, China [2] Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China [3] Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of China, Beijing, China.
authors.forename: Ke
authors.initials: K
authors.lastname: He
authors.affiliation: 1] Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of China, Beijing, China [2] Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China [3] Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of China, Beijing, China.
authors.forename: Huan-Na
authors.initials: HN
authors.lastname: Mu
authors.affiliation: 1] Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of China, Beijing, China [2] Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China [3] Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of China, Beijing, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Li
authors.affiliation: 1] Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of China, Beijing, China [2] Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China [3] Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of China, Beijing, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Sun
authors.affiliation: 1] Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of China, Beijing, China [2] Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China [3] Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of China, Beijing, China.
authors.forename: Jing-Yu
authors.initials: JY
authors.lastname: Fan
authors.affiliation: 1] Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China [2] Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of China, Beijing, China [3] Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China [4] Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of China, Beijing, China.
authors.forename: Jing-Yan
authors.initials: JY
authors.lastname: Han
mesh_terms: D000818:Animals; D001600:Berberine Alkaloids / Q000494:pharmacology*; D001812:Blood-Brain Barrier / Q000187:drug effects*; D002545:Brain Ischemia / Q000201:enzymology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D001600:Berberine Alkaloids; C014215:tetrahydropalmatine; D019061:src-Family Kinases