Penehyclidine hydrochloride inhibits TLR4 signaling and inflammation, and attenuates blunt chest trauma and hemorrhagic shock-induced acute lung injury in rats

Wu,Xiao‑Jing; Liu,Hui‑Min; Song,Xue‑Min; Zhao,Bo; Leng,Yan; Wang,E‑You; Zhan,Li‑Ying; Meng,Qing‑Tao; Xia,Zhong‑Yuan

doi:10.3892/mmr.2018.8644

Penehyclidine hydrochloride inhibits TLR4 signaling and inflammation, and attenuates blunt chest trauma and hemorrhagic shock-induced acute lung injury in rats

Authors:
- Xiao‑Jing Wu
- Hui‑Min Liu
- Xue‑Min Song
- Bo Zhao
- Yan Leng
- E‑You Wang
- Li‑Ying Zhan
- Qing‑Tao Meng
- Zhong‑Yuan Xia
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Affiliations: Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China, Department of Anesthesiology and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China
Published online on: February 27, 2018 https://doi.org/10.3892/mmr.2018.8644
Pages: 6327-6336
Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Blunt chest trauma with hemorrhagic shock (THS) frequently induces pulmonary inflammation that leads to acute lung injury (ALI). Penehyclidine hydrochloride (PHC) possesses anti‑inflammatory properties that may attenuate the systemic inflammatory response. The present study aimed to evaluate the molecular mechanism of PHC in modifying THS‑induced ALI in rats. Rats underwent either THS or a sham procedure. At 6 h subsequent to blunt chest trauma, arterial blood was drawn for blood gas and pro‑inflammatory factors analyses, and lung tissue samples were collected to examine pulmonary histopathological alterations, the wet/dry weight ratio, myeloperoxidase activity, and the protein expression levels of Toll-like receptor 4 (TLR4), phosphorylated (p‑)p38 mitogen‑activated protein kinase (MAPK), nuclear factor (NF)‑κB and activator protein‑1 (AP‑1). THS caused significant reductions in heart rate and mean arterial blood pressure, and was associated with significant increases in tumor necrosis factor‑α, interleukin (IL)‑6, IL‑1β, p‑p38MAPK, NF‑κB and AP‑1 activation, in addition to TLR4 expression, in the lung. PHC effectively attenuated THS‑induced ALI, and inhibited TLR4 expression, reduced the activation of p‑p38MAPK, NF‑κB and AP‑1, and downregulated the expression of pro‑inflammatory mediators. In conclusion, the results of the present study demonstrated that PHC may exert an anti‑inflammatory effect and attenuate THS‑induced ALI by inhibiting the TLR4 signaling pathway. These preclinical findings may offer a novel therapeutic strategy to restrict TLR4 overactivation in ALI.

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