Ulinastatin protects the lungs of COPD rats through the HMGB1/TLR4 signaling pathway

Liu,Wei; Liu,Zhiguang; Zhang,Weidong; Cai,Shaoxi

doi:10.3892/ol.2018.9123

Ulinastatin protects the lungs of COPD rats through the HMGB1/TLR4 signaling pathway

Authors:
- Wei Liu
- Zhiguang Liu
- Weidong Zhang
- Shaoxi Cai
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Affiliations: Chronic Airway Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China, Department of Respiratory Medicine, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan 410005, P.R. China
Published online on: July 11, 2018 https://doi.org/10.3892/ol.2018.9123
Pages: 4057-4063

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Abstract

The present study aimed to investigate the protective mechanism of ulinastatin against lung injury. Rat models with chronic obstructive pulmonary disease (COPD) were used to provide guidance for the medical treatment of this disease. The rats were divided into three groups: A control group, a model group and an experimental group (each, n=10). With the exception of the control group, all of the rats were prepared as models of COPD, using the composite molding method of smoking and intratracheal instillation of lipopolysaccharide. The rats in the model group all received a conventional treatment, while the rats in the experimental group received ulinastatin. A small animal lung function detector was used to examine lung function. The forced expiratory volume/sec (FEV) was negatively correlated with the protein expression levels of Toll‑like receptor 4 (TLR4) and high mobility group box protein 1 (HMGB1). Real‑time fluorescence quantitative polymerase chain reaction and western blot analyses were used to detect TLR4, MyD88 (myeloid differentiation factor 88), TRAF‑6 (TNF receptor‑associated factor 6), LOX‑1 (lectin‑type oxidized LDL receptor 1) and HMGB1 mRNA, along with their protein expression levels. The lung function of rats in the model group was significantly decreased compared with in the control group (P<0.05). In the experimental group the lung function was significantly greater, when compared with in the model group; however, it remained lower than in the control group. The mRNA and protein expression levels of TLR4, MyD88, TRAF‑6, LOX‑1 and HMGB1 were significantly higher in the model group than in the control and experimental groups; however, levels in the experimental group were significantly higher when compared with in the control group (P<0.05). The TLR4 and HMGB1 expression levels were positively correlated in all groups, which indicated involvement of the HMGB1/TLR4 signaling pathway. The FEV was negatively correlated with the protein expression levels of TLR4 and HMGB1. Thus, the protective effect of ulinastatin in the lungs of rats with COPD is associated with changes in the HMGB1/TLR4 signaling pathway.

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