The Clinical Significance of iNOS/NO Signaling Pathway in Traumatic Shock and the Mechanism under the Promotion on the Development of Traumatic Shock via Endoplasmic Reticulum Stress.

Abstract

Objective: This study aims to clarify the clinical significance of the inducible nitric oxide synthase (iNOs)/nitric oxide (NO) signaling pathway and endoplasmic reticulum stress (ERS) in traumatic shock (TS) and the mechanism of action, so as to offer a novel direction for the emergency treatment of TS in the future.

Methods: The clinical data of 90 patients with TS treated in our hospital between June 2019 and January 2021 were retrospectively analyzed. Patients were divided into mild (n = 30), moderate (n = 30), and severe group (n = 30) based on their disease severity. Furthermore, patients were assigned into Groups A and B for fluid resuscitation based on a pulse index continuous cardiac output (PICCO) monitor and fluid resuscitation based on monitoring results of central venous pressure (CVP) and mean arterial pressure (MAP), respectively. Additionally, the 18 purchased Sprague Dawley (SD) rats were randomized into model (TS model), control (normal rats) and intervention (TS model injected with iNOS inhibitor) groups, with 6 rats each. iNOs and NO levels were measured by colorimetry, and the concentrations of inflammatory factors were quantified using enzyme-linked immunosorbent assays (ELISAs). Polymerase chain reaction (PCR) and western blot were adopted for the quantification of ERS markers (glucose-related protein 78 (GRP78), GRP94 and C/EBP homologous protein (CHOP)), and hematoxylin-eosin (HE) staining of rat cardiac tissue was carried out to observe the pathological state of myocardial tissue.

Results: The moderate group showed higher levels of iNOS, NO, GRP78, GRP94 and CHOP than the mild group and lower levels of them than the severe group (all p < 0.05). MAP, extravascular lung water index (EVLWI), pulmonary vascular permeability index (PVPI), and locus control region (LCR) increased in both Groups A and B after resuscitation, with more significant increases of these parameters in Group A. The application of PICCO technique lowered the levels of iNOS, NO, inflammatory factors, GRP78, GRP94 and CHOP in TS patients. In addition, the intervention group had lower levels of iNOS, NO, inflammatory factors, GRP78, GRP94, and CHOP than the model group and higher levels of them than the control group. According to the results of HE staining of myocardial tissue, the intervention group had significantly alleviated myocardial necrosis than the model group, with slightly stained cytoplasm, visible contraction bands in most myocardium, and significantly reduced neutrophil infiltration.

Conclusions: iNOS/NO and ERS increase with the severity of TS, and PICCO can effectively lower their levels. The results of animal experiments suggest that the inhibition of iNOS/NO can relieve inflammation and ERS intensification, thus alleviating the progression of TS.