title: Therapeutic effects of neuregulin-1 in diabetic cardiomyopathy rats.
abstract: BACKGROUND
  Diabetic cardiomyopathy (DCM) is a disorder of the heart muscle in people with diabetes, which is characterized by both systolic and diastolic dysfunction. The effective treatment strategy for DCM has not been developed.
  
  
  METHODS
  Rats were divided into 3 groups with different treatment. The control group was only injected with citrate buffer (n = 8). The diabetes group and diabetes treated group were injected with streptozotocin to induce diabetes. After success of diabetes induction, the rats with diabetes were treated with (diabetes treated group, n = 8) or without (diabetes group, n = 8) recombinant human Neuregulin-1 (rhNRG-1). All studies were carried out 16 weeks after induction of diabetes. Cardiac catheterization was performed to evaluate the cardiac function. Apoptotic cells were determined by TUNEL staining. Left ventricular (LV) sections were stained with Masson to investigate myocardial collagen contents. Related gene expressions were analyzed by quantitative real-time PCR (qRT-PCR).
  
  
  RESULTS
  Diabetes impaired cardiac function manifested by reduced LV systolic pressure (LVSP), maximum rate of LV pressure rise and fall (+dp/dt max and -dp/dt max) and increased LV end-diastolic pressure (LVEDP). The rhNRG-1 treatment could significantly alleviate these symptoms and improve heart function. More TUNEL staining positive cells were observed in the diabetic group than that in the control group, and the rhNRG-1 treatment decreased apoptotic cells number. Furthermore, qRT-PCR assay demonstrated that rhNRG-1 treatment could decrease the expression of bax and caspase-3 and increase that of bcl-2. Collagen volume fraction was higher in the diabetic group than in the control group. Fibrotic and fibrotic related mRNA (type I and type III collagen) levels in the myocardium were significantly reduced by administration of rhNRG-1.
  
  
  CONCLUSIONS
  rhNRG-1 could significantly improve the heart function and reverse the cardiac remodeling of DCM rats with chronic heart failure. These results support the clinical possibility of applying rhNRG-1 as an optional therapeutic strategy for DCM treatment in the future.
authors.affiliation: Department of Cardiology, First Affiliated Hospital, Nanchang University, Nanchang 330006, China. lbg2210@tom.com
authors.forename: Bingong
authors.initials: B
authors.lastname: Li
authors.forename: Zeqi
authors.initials: Z
authors.lastname: Zheng
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Wei
authors.forename: Menghong
authors.initials: M
authors.lastname: Wang
authors.forename: Jingtian
authors.initials: J
authors.lastname: Peng
authors.forename: Ting
authors.initials: T
authors.lastname: Kang
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.forename: Jian
authors.initials: J
authors.lastname: Xiao
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.forename: Zhe
authors.initials: Z
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002908:Chronic Disease; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications*; D058065:Diabetic Cardiomyopathies / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D009206:Myocardium / Q000473:pathology; D020890:Neuregulin-1 / Q000494:pharmacology / Q000627:therapeutic use*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D013311:Streptozocin / Q000009:adverse effects; D016896:Treatment Outcome; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D020890:Neuregulin-1; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D051028:bcl-2-Associated X Protein; D013311:Streptozocin; D053148:Caspase 3