title: Salvianolic Acid B Ameliorates Lipopolysaccharide-Induced Albumin Leakage from Rat Mesenteric Venules through Src-Regulated Transcelluar Pathway and Paracellular Pathway.
abstract: Lipopolysaccharide (LPS) causes microvascular barrier disruption, leading to albumin leakage from microvessels resulting in a range of disastrous sequels. Salvianolic acid B (SalB) is a major water-soluble component derived from Salvia miltiorrhiza. Previous studies showed its potential to attenuate microvascular barrier dysfunction, but the underlying mechanism is not fully understood. The present study was intended to investigate the impact of SalB on endothelial cell barrier in vivo in rat mesenteric venules as well as in vitro in human umbilical vein endothelial cells (HUVECs), aiming at disclosing the mechanism thereof, particularly the role of Src in its action. Male Wistar rats were challenged by infusion of LPS (2 mg/kg/h) through left femoral vein for 90 min. SalB (5 mg/kg/h) was administrated either simultaneously with LPS or 30 min after LPS infusion through the left jugular vein. Vesicles in venular walls were observed by electron microscopy. HUVECs were incubated with LPS with or without SalB. The expression of Zonula occluden-1 (ZO-1), VE-cadherin, caveolin-1 and Src in HUVECs was assessed by Western blot and confocal microscopy, binding of SalB to Src was measured using Surface Plasmon Resonance and BioLayer Interferometry. Treatment with SalB inhibited albumin leakage from rat mesenteric venules and inhibited the increase of vesicle number in venular endothelial cells induced by LPS. In addition, SalB inhibited the degradation of ZO-1, the phosphorylation and redistribution of VE-cadherin, the expression and phosphorylation of caveolin-1, and phosphoirylation of Src in HUVECs exposed to LPS. Furthermore, SalB was found able to bind to Src. This study demonstrates that protection of SalB against microvascular barrier disruption is a process involving both para- and trans-endothelial cell pathway, and highly suggests Src as the key enzyme for SalB to work.
authors.affiliation: Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China; Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of the People's Republic of China, Beijing, China; Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People's Republic of China, Beijing, China.
authors.forename: Chun-Shui
authors.initials: CS
authors.lastname: Pan
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital& Institute, Beijing, China.
authors.forename: Ying-Hua
authors.initials: YH
authors.lastname: Liu
authors.affiliation: Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China; Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of the People's Republic of China, Beijing, China; Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People's Republic of China, Beijing, China.
authors.forename: Yu-Ying
authors.initials: YY
authors.lastname: Liu
authors.affiliation: Department of Integration of Traditional Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China; Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of the People's Republic of China, Beijing, China; Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People's Republic of China, Beijing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Integration of Traditional Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China; Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of the People's Republic of China, Beijing, China; Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People's Republic of China, Beijing, China.
authors.forename: Ke
authors.initials: K
authors.lastname: He
authors.affiliation: Department of Integration of Traditional Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China; Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of the People's Republic of China, Beijing, China; Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People's Republic of China, Beijing, China.
authors.forename: Xiao-Yuan
authors.initials: XY
authors.lastname: Yang
authors.affiliation: Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China; Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of the People's Republic of China, Beijing, China; Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People's Republic of China, Beijing, China.
authors.forename: Bai-He
authors.initials: BH
authors.lastname: Hu
authors.affiliation: Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China; Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of the People's Republic of China, Beijing, China; Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People's Republic of China, Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Chang
authors.affiliation: Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China; Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of the People's Republic of China, Beijing, China; Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People's Republic of China, Beijing, China.
authors.forename: Ming-Xia
authors.initials: MX
authors.lastname: Wang
authors.affiliation: Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China.
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Wei
authors.affiliation: Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China.
authors.forename: Jing-Yu
authors.initials: JY
authors.lastname: Fan
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital& Institute, Beijing, China.
authors.forename: Xin-Min
authors.initials: XM
authors.lastname: Wu
authors.affiliation: Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China; Department of Integration of Traditional Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China; Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of the People's Republic of China, Beijing, China; Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People's Republic of China, Beijing, China.
authors.forename: Jing-Yan
authors.initials: JY
authors.lastname: Han
mesh_terms: D000418:Albumins / Q000378:metabolism*; D000818:Animals; D001572:Benzofurans / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008642:Mesenteric Veins / Q000378:metabolism*; D010766:Phosphorylation; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014699:Venules / Q000378:metabolism; D053630:Depsides
chemical_list: D000418:Albumins; D001572:Benzofurans; D008070:Lipopolysaccharides; D016392:Proto-Oncogene Proteins pp60(c-src); C076944:salvianolic acid B; D053630:Depsides