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

Molecular Medicine Reports
Xiao-Jing WuZhong-Yuan Xia

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‑...Continue Reading

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Citations

Jun 8, 2019·American Journal of Physiology. Heart and Circulatory Physiology·Zahra Tavakoli Dargani, Dinender K Singla
Dec 8, 2020·Oxidative Medicine and Cellular Longevity·Yang LiuYanfeng Wang
May 4, 2021·Frontiers in Immunology·Namrita Halder, Girdhari Lal

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Methods Mentioned

BETA
protein assay
ELISA
electron microscopy

Software Mentioned

2000
HIPAS
SPSS

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