title: Glaucocalyxin A Ameliorates Myocardial Ischemia-Reperfusion Injury in Mice by Suppression of Microvascular Thrombosis.
abstract: BACKGROUND The aim of this study was to evaluate the cardio-protective roles of glaucocalyxin A (GLA) in myocardial ischemia-reperfusion injury and to explore the underlying mechanism. MATERIAL AND METHODS Myocardial ischemia-reperfusion in wild-type C57BL/6J mice was induced by transient ligation of the left anterior descending artery. GLA or vehicle (solvent) was administrated intraperitoneally to the mice before reperfusion started. After 24 h of myocardial reperfusion, ischemic size was revealed by Evans blue/TTC staining. Cardiac function was evaluated by echocardiography and microvascular thrombosis was assessed by immunofluorescence staining of affected heart tissue. We also measured the phosphorylation of AKT, ERK, P-GSK-3β, and cleaved caspase 3 in the myocardium. RESULTS Compared to the solvent-treated control group, GLA administration significantly reduced infarct size (GLA 13.85±2.08% vs. Control 18.95±0.97%, p<0.05) and improved left ventricular ejection fraction (LVEF) (GLA 53.13±1.11% vs. Control 49.99±1.25%, p<0.05) and left ventricular fractional shortening (LVFS) (28.34±0.71% vs. Control 25.11±0.74%, p<0.05) in mice subjected to myocardial ischemia-reperfusion. GLA also attenuated microvascular thrombosis (P<0.05) and increased the phosphorylation of pro-survival kinase AKT (P<0.05) and GSK-3β (P<0.05) in the myocardium upon reperfusion injury. CONCLUSIONS Administration of GLA before reperfusion ameliorates myocardial ischemia-reperfusion injury in mice. The cardio-protective roles of GLA may be mediated through the attenuation of microvascular thrombosis.
authors.affiliation: Cyrus Tang Hematology Center, Soochow University, Suzhou, Jiangsu, China (mainland).
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Liu
authors.affiliation: Cyrus Tang Hematology Center, Soochow University, Suzhou, Jiangsu, China (mainland).
authors.forename: Dongzhou
authors.initials: D
authors.lastname: Xu
authors.affiliation: Department of Pathology, Jilin Hospital of Chinese Armed Police Force, Changchun, Jilin, China (mainland).
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Cyrus Tang Hematology Center, Soochow University, Suzhou, Jiangsu, China (mainland).
authors.forename: Ting
authors.initials: T
authors.lastname: Chen
authors.affiliation: Cyrus Tang Hematology Center, Soochow University, Suzhou, Jiangsu, China (mainland).
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China (mainland).
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Cyrus Tang Hematology Center, Soochow University, Suzhou, Jiangsu, China (mainland).
authors.forename: Tao
authors.initials: T
authors.lastname: You
authors.affiliation: Cyrus Tang Hematology Center, Soochow University, Suzhou, Jiangsu, China (mainland).
authors.forename: Li
authors.initials: L
authors.lastname: Zhu
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology; D003331:Coronary Vessels / Q000503:physiopathology; D045786:Diterpenes, Kaurane / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism; D015398:Signal Transduction; D013927:Thrombosis / Q000188:drug therapy* / Q000378:metabolism; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D002316:Cardiotonic Agents; D045786:Diterpenes, Kaurane; C055124:glaucocalyxin A