title: [Long-term effects of heme oxygenase 1 overexpression on post-infarction heart function in diabetic rats].
abstract: OBJECTIVE
  To clarify the impact of increased heme oxygenase-1 (HO-1) expression on cardiac function of diabetic rats with myocardial infarction and its mechanism.
  
  
  METHODS
  Sixty adult male Wistar rats were randomly divided into five groups (n = 12): sham operation group (sham), diabetes + sham operation group (DM + sham), diabetes + MI group (DM + MI) , diabetes + myocardial infarction + cobalt original porphyrin (CoPP) group (DM + MI + CoPP), diabetes + myocardial infarction + CoPP+ tin porphyrin (SnMP) group (DM + MI + CoPP + SnMP). CoPP 4.5 mg/kg or SnMP 15 mg/kg were administered at the day next to MI operation, for six weeks, once a week. At the 28th week post operation, the echocardiography, left heart via the carotid artery indoor intubation were used to observe the long-term influence of HO-1 inducer (cobalt protoporphyrin, CoPP) and activity of HO inhibitor (tin porphyrin, SnMP) on the indices of left ventricular remodeling and cardiac function after the intervention. Blood glucose (GLU), total cholesterol (TC), C-reactive protein (CRP), serum creatinine (Cr), aminotransferase (ALT) and other indicators were measured. ELISA was used to test interleukin-6 (IL-6), tumor necrosis factor (TNF), nitric oxide (NO), prostacyclin (PGI2), adiponectin, and ultra sensitive CRP (HsCRP) level.
  
  
  RESULTS
  HO-1 inducer, CoPP, could ameliorate ± dp/dtmax, left ventricular ejection fraction and left ventricular shortening fraction in diabetic myocardial infarction rats. It could also decrease left ventricular end-diastolic diameter. The serum bilirubin, NO and PGI2 levels, myocardial phosphorylated endothelial nitric oxide synthasee(peNOS), phosphorylated activated protein kinase (pAkt), phosphorylated adenosine monophosphate-activated protein kinase (pAMPK) expression were also significantly elevated, and the serum hs-CRP and TNF levels were significantly inhibited. Compared to inducer group, cardiac function were worse in the inhibitor group.
  
  
  CONCLUSIONS
  Upregulated HO-1 level can improve the endothelial function, inhibite of the inflammatory response and enhance the antioxidant substances in serum bilirubin via peNOS-pAMPK pathway, which effectively inhibit ventricular remodeling and improve the long-term cardiac function after infarction in diabetic rats.
authors.affiliation: The First Department of Geriatric Cardiology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Tian-Meng
authors.initials: TM
authors.lastname: Chen
authors.forename: Jianla
authors.initials: J
authors.lastname: Cao
authors.forename: De-You
authors.initials: DY
authors.lastname: Chen
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Shi
authors.forename: Meng
authors.initials: M
authors.lastname: Gao
authors.lastname: Fan Li
authors.forename: Nader G
authors.initials: NG
authors.lastname: Abraham
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001663:Bilirubin / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D008297:Male; D009203:Myocardial Infarction / Q000201:enzymology*; D009206:Myocardium / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D015854:Up-Regulation; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D001663:Bilirubin