title: The protective role of neuregulin-1: A potential therapy for sepsis-induced cardiomyopathy.
abstract: The extremely high mortality of sepsis in intensive care units, caused primarily by sepsis-induced cardiomyopathy, is a pressing issue. Current studies have revealed the importance of the neuregulin-1 (NRG-1)/ErbB signaling axis at the cardiovascular level and the positive effect of NRG-1 on cardiac function in patients with heart failure. To investigate the protective mechanism of NRG-1 against myocardial injury in septic rats, a cecal ligation and puncture (CLP) model was applied. Animals were administered either a vehicle or recombinant human NRG-1 (rhNRG-1, 10μg/kg). Their survival rates were noted 24h after CLP. The hemodynamic method was used to evaluate their cardiac function. The myocardial morphology was observed. An enzyme-linked immunosorbent assay was used to detect the level of cardiac troponin-T (cTn-T), cytokines, and angiotensin II (Ang II) in the serum and myocardium. Compared with the vehicle, rhNRG-1 improved survival of rats and prevented hemodynamic derangement, as reflected in the increased mean arterial pressure, left ventricular systolic pressure, ±dp/dt max, and decreased left ventricular end-diastolic pressure (P<0.05). Furthermore, the serum levels of cTn-T and pro-inflammatory cytokines (tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, and IL-6) were significantly increased in vehicle-treated rats but reduced in rhNRG-1-treated rats. The latter also showed decreased concentration of macrophage inhibitory factor and Ang II in the myocardium (P<0.05). These results suggest that NRG-1 improved cardiac function and protected cardiomyocytes of rats from CLP-induced sepsis by suppressing the immune inflammatory response and excessive activation of the renin-angiotensin-aldosterone system. Ultimately, NRG-1 increased the survival rate of rats.
authors.affiliation: Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, PR China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, PR China.
authors.forename: Xia
authors.initials: X
authors.lastname: Pan
authors.affiliation: Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, PR China. Electronic address: wanglongwhu@163.com.
authors.forename: Long
authors.initials: L
authors.lastname: Wang
authors.affiliation: Cardiovascular Research Institute of Wuhan University, Wuhan, PR China. Electronic address: xiwangwhu@163.com.
authors.forename: Xi
authors.initials: X
authors.lastname: Wang
authors.affiliation: Cardiovascular Research Institute of Wuhan University, Wuhan, PR China.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Xiong
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D009202:Cardiomyopathies / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D002316:Cardiotonic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D020890:Neuregulin-1 / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000187:drug effects; D018805:Sepsis
chemical_list: D015415:Biomarkers; D002316:Cardiotonic Agents; D020890:Neuregulin-1
keywords: Angiotensin II; Cardiac function; Inflammation; Macrophage inhibitory factor; Neuregulin-1; Sepsis