title: Salvianolate reduces murine myocardial ischemia and reperfusion injury via ERK1/2 signaling pathways in vivo.
abstract: OBJECTIVE
  To analyze the effects of salvianolate on myocardial infarction in a murine in vivo model of ischemia and reperfusion (I/R) injury.
  
  
  METHODS
  Myocardial I/R injury model was constructed in mice by 30 min of coronary occlusion followed by 24 h of reperfusion and pretreated with salvianolate 30 min before I/R (SAL group). The SAL group was compared with SHAM (no I/R and no salvianolate), I/R (no salvianolate), and ischemia preconditioning (IPC) groups. Furthermore, an ERK1/2 inhibitor PD98059 (1 mg/kg), and a phosphatidylinositol-3-kinase (PI3-K) inhibitor, LY294002 (7.5 mg/kg), were administered intraperitoneal injection (i.p) for 30 min prior to salvianolate, followed by I/R surgery in LY and PD groups. By using a double staining method, the ratio of the infarct size (IS) to left ventricle (LV) and of risk region (RR) to LV were compared among the groups. Correlations between IS and RR were analyzed. Western-blot was used to detect the extracellular signal-regulated kinase 1/2 (ERK1/2) and protein kinase B (AKT) phosphorylation changes.
  
  
  RESULTS
  There were no significant differences between RR to LV ratio among the SHAM, I/R, IPC and SAL groups (P>0.05). The SAL and IPC groups had IS of 26.1%±1.4% and 22.3%±2.9% of RR, respectively, both of which were significantly smaller than the I/R group (38.5%±2.9% of RR, P<0.05, P<0.01, respectively). Moreover, the phosphorylation of ERK1/2 was increased in SAL group (P<0.05), while AKT had no significant change. LY294002 further reduced IS, whereas the protective role of salvianolate could be attenuated by PD98059, which increased the IS. Additionally, the IS was not linearly related to the RR (r=0.23, 0.45, 0.62, 0.17, and 0.52 in the SHAM, I/R, SAL, LY and PD groups, respectively).
  
  
  CONCLUSIONS
  Salvianolate could reduce myocardial I/R injury in mice in vivo, which involves an ERK1/2 pathway, but not a PI3-K signaling pathway.
authors: Intensive Care Laboratory, Guangdong Province Hospital of Chinese Medicine, 2nd Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, China.
authors: Jian-Yong
authors: JY
authors: Qi
authors: Animal Laboratory, Guangdong Province Hospital of Chinese Medicine, 2nd Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
authors: Juan
authors: J
authors: Yu
authors: Intensive Care Laboratory, Guangdong Province Hospital of Chinese Medicine, 2nd Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, China.
authors: Dong-Hui
authors: DH
authors: Huang
authors: Intensive Care Laboratory, Guangdong Province Hospital of Chinese Medicine, 2nd Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, China.
authors: Li-Heng
authors: LH
authors: Guo
authors: Intensive Care Laboratory, Guangdong Province Hospital of Chinese Medicine, 2nd Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, China.
authors: Lei
authors: L
authors: Wang
authors: Intensive Care Laboratory, Guangdong Province Hospital of Chinese Medicine, 2nd Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, China.
authors: Xin
authors: X
authors: Huang
authors: Animal Laboratory, Guangdong Province Hospital of Chinese Medicine, 2nd Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
authors: Hai-Ding
authors: HD
authors: Huang
authors: Department of Oral and Maxillary Surgery, Stomatology Hospital of Guangzhou Medical University, Guangzhou, 510006, China.
authors: Miao
authors: M
authors: Zhou
authors: Intensive Care Laboratory, Guangdong Province Hospital of Chinese Medicine, 2nd Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, China. minzhouzhang8@163.com.
authors: Min-Zhou
authors: MZ
authors: Zhang
authors: Northeast Ohio Medical University, Rootstown, Ohio, USA.
authors: Jiashin
authors: J
authors: Wu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use; D005419:Flavonoids / Q000494:pharmacology; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D013194:Staining and Labeling
chemical_list: D002316:Cardiotonic Agents; D005419:Flavonoids; D010936:Plant Extracts; D047428:Protein Kinase Inhibitors; C561960:salvianolate; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
keywords: Chinese medicine; extracellular signal-regulated kinase 1/2; ischemia and reperfusion injury; protein kinase B; salvianolate