ABSTRACT
Objective To explore the protective effect of neuregulin-1 (NRG-1) on heart function and myocardium in rats with sepsis and its mechanism . Methods Healthy male Sprague-Dawly (SD) rats were divided into three groups according to random number table method, with 6 rats in each group. Sepsis model was established by cecal ligation and puncture (CLP group); rats in sham operation group (sham group) underwent the same procedure except ligation. Rats in NRG-1 pre-treatment group (NRG group) were intravenously injected with recombinant human NGR-1 (rhNRG-1) at the dose of 10 μg/kg through tail vein; rats in CLP group and sham group were treated with the same amount of saline. At 24 hours after CLP, hemodynamic method was used to evaluate the cardiac function, and myocardial morphology was observed with hematoxylin and eosin (HE) staining, enzyme linked immunosorbent assay (ELISA) was used to detect the levels of cardiac troponin T (cTnT), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) in serum and macrophage migration inhibitor factor (MIF) in myocardial tissue. Results ① heart function: compared with the sham group, the mean arterial pressure (MAP), left ventricular systolic pressure (LVSP) and left ventricular pressure maximal rate of rise and fall (±dp/dt max) were significantly decreased in CLP group and NRG group, while the MAP, LVSP and ±dp/dt max in NRG group were significantly higher than those in CLP group [MAP (mmHg, 1 mmHg = 0.133 kPa): 125.78±8.15 vs. 113.05±5.85, LVSP (mmHg): 151.27±6.79 vs. 139.39±8.05, +dp/dt max (kPa/s): 4 389.59±332.38 vs. 3 706.85±451.31, -dp/dt max (kPa/s): 4 291.42±323.72 vs. 3 691.17±515.44, all 1 <0.05]. ②Myocardial injury: compared with the sham group, the levels of serum cTnT in CLP group and NRG group were significantly increased, while the levels of serum cTnT in NRG group were significantly lower than those in CLP group (ng/L: 206.37±67.28 vs. 344.13±80.95, 1 < 0.05), and the HE staining showed that myocardial pathological changes in NRG group were improved compared with the CLP group. ③Inflammatory mediators level: compared with the sham group, the levels of serum TNF-α, IL-1β and myocardial MIF were significantly increased in CLP group and NRG group, while the indicators in NRG group were lower than those in CLP group [TNF-α(ng/L): 52.77±3.43 vs. 97.19±13.98, IL-1β (ng/L): 40.25±5.48 vs. 56.05±6.88, MIF (μg/L): 1.92±0.16 vs. 2.87±0.10, all 1 <0.05]. Conclusion NRG-1 can reduce circulating levels of inflammatory factors in rats with sepsis, adjust myocardial MIF level, and alleviate myocardial cell injury, thereby improving cardiac function, and play a role in myocardial protection.