Upregulation of endoplasmic reticulum stress is associated with diaphragm contractile dysfunction in a rat model of sepsis

Jiao,Guangyu; Hao,Liying; Wang,Mengmeng; Zhong,Bin; Yu,Miao; Zhao,Shuang; Wang,Pingping; Feng,Rui; Tan,Shutao; Chen,Liu

doi:10.3892/mmr.2016.6014

Upregulation of endoplasmic reticulum stress is associated with diaphragm contractile dysfunction in a rat model of sepsis

Authors:
- Guangyu Jiao
- Liying Hao
- Mengmeng Wang
- Bin Zhong
- Miao Yu
- Shuang Zhao
- Pingping Wang
- Rui Feng
- Shutao Tan
- Liu Chen
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Affiliations: Respiratory Department and Intensive Care Unit, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China, Department of Pharmaceutical Toxicology, School of Pharmaceutical Sciences, China Medical University, Shenyang, Liaoning 110001, P.R. China
Published online on: December 9, 2016 https://doi.org/10.3892/mmr.2016.6014
Pages: 366-374

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Abstract

Sepsis often causes diaphragm contractile dysfunction. Endoplasmic reticulum (ER) stress has been implicated in muscle contractile dysfunction. However, it remains unknown if ER stress occurs in the diaphragm during sepsis. In the present study, rats were divided into 4 groups and received placebo or one of three durations of endotoxin treatment (24, 48 h and 7 days). Isometric contractile force of the diaphragm was measured and lung wet-to-dry ratio (W/D) was calculated. Hematoxylin and eosin (H&E) staining of lung tissue was performed and electron microscopy assessed ER damage in the diaphragm during sepsis. The mRNA and protein expression of glucose‑regulated protein 78 kDa (GRP78), glucose-regulated protein 94 kDa (GRP94), C/EBP homologous protein (CHOP), endoplasmic reticulum protein 44 (ERP44), protein disulfide-isomerase like protein (ERP57) and protein disulfide isomerase family A member 4 (ERP72) in diaphragm muscles were measured using reverse transcription‑quantitative polymerase chain reaction and western blot analysis. The level of cleaved caspase-12 was analyzed by western blot analysis. The results demonstrated that sepsis increased lung W/D. H&E staining revealed that sepsis caused alveolar congestion, hemorrhage and rupture. Swollen and distended ER was observed using electron microscopy during sepsis and decreased diaphragm contractile function was also observed. The expression levels of ER stress markers (GRP78, GRP94, CHOP, ERP44, ERP57 and ERP72) and the level of cleaved caspase‑12 were significantly elevated in septic rats compared with control rats, particularly in the 48 h group. In conclusion, the present study indicated that weakened diaphragm contraction and damaged ER in septic rats was associated with increased expression of ER stress markers.

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