title: [In vitro study on the mechanism of myocardial injury induced by Formoterol and the protective effect of Budesonide in rats].
abstract: OBJECTIVE
  To investigate the mechanism of myocardial injury induced by Formoterol (FORM) in vitro and the protective effect of Budesonide (BUD) against such cardiac damage in rats.
  
  
  METHODS
  FORM was added in the media of isolated rat myocardial tissues in a concentration gradients of 0 μmol/L, 0.01 μmol/L, 0.05 μmol/L, 0.1 μmol/L, 0.5 μmol/L, 1 μmol/L, 5 μmol/L, respectively, or combined with BUD in a concentration of 10 μmol/L, for 72 hours in vitro. The cardiac troponin I (cTnI) and heart-type fatty acid-binding protein (H-FABP) in supernatant were detected with ELISA method. The mRNA level of glycogen synthase kinase-3β (GSK-3β) was detected with RT-PCR. Sarco(endo) plasmic reticulum Ca(2+);-ATPase (SERCA2) and GSK-3β protein expression were detected with Western blot.
  
  
  RESULTS
  (1) The values of cTnI and H-FABP were significantly higher in FORM groups, compared with the control group(P<0.05), and there was a difference between different FORM concentration gradients (P<0.05) except 1 μmol/L and 5 μmol/L groups. In FORM and BUD combined groups, the values of cTnI and H-FABP were significantly lower than FORM groups(P<0.05). (2) With the increase of FORM concentration, there were lower expression of SERCA2 (P<0.05) and higher expression of GSK-3β protein (P<0.05). But there was no significant statistic difference of GSK-3β mRNA between FORM treated groups (P>0.05).
  
  
  CONCLUSIONS
  (1) FORM can induce injury in rat's isolated myocardial tissues and the injury is concentration depended. BUD shows protective effect against FORM induced myocardial injury. (2) The mechanism of FORM induced myocardial injury may be associated with the lower expression of SERCA2, which is mediated by GSK-3β.
authors.affiliation: Organization for Drug Clinical Trial, Institute of Clinical Pharmacology, West China Hospital, Sichuan University, Chengdu 610041, China. LF20080501@126.com
authors.forename: Fen
authors.initials: F
authors.lastname: Liu
authors.forename: Chun-tao
authors.initials: CT
authors.lastname: Liu
mesh_terms: D000818:Animals; D019819:Budesonide / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004983:Ethanolamines / Q000633:toxicity*; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins / Q000187:drug effects* / Q000378:metabolism; D000068759:Formoterol Fumarate; D038362:Glycogen Synthase Kinase 3 / Q000187:drug effects* / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006321:Heart / Q000187:drug effects*; D009206:Myocardium / Q000201:enzymology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000187:drug effects* / Q000378:metabolism; D019210:Troponin I / Q000187:drug effects* / Q000378:metabolism
chemical_list: C506948:Atp2a2 protein, rat; D004983:Ethanolamines; C509948:FABP3 protein, rat; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins; D012333:RNA, Messenger; D019210:Troponin I; D019819:Budesonide; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000068759:Formoterol Fumarate