A modified "double-hit" induced acute lung injury model in rats and protective effects of tetramethylpyrazine on the injury via Rho/ROCK pathway.

Abstract

We focused on the production and evaluation of a modified "double-hit" induced acute lung injury (ALI) model, which closely mimics the clinical situation. Further, tetramethylpyrazine (TMP), an alkaloid contained in ligustrazine was evaluated for its potent anti-inflammatory effects in this model. Rats were randomized into 4 groups: G1 (NS control group), G2 ("double-hit" group), G3 (low dosage TMP group) and G4 (high dosage TMP group). The rats in G2, G3 and G4 were intraperitoneally injected with a low dose of LPS followed by intratracheal injection with median dose of LPS to establish the "double-hit" model. The rats in G3, G4 were intraperitoneally injected with low (G3), high (G4) dosage TMP for the protection against ALI. Upon termination of the experiment, TMP attenuated the harmful changes in animal model reaction, breathing frequency, histological examination, lung W/D-weight ratio, BAL fluid PMNs percentage, MPO activity and ROCK2 mRNA expression. We found inhibiting RhoA/ROCK pathway might attribute to TMP-induced protection against ALI.

• Authors: Shidi Zhao, Yong Zhang, Qianfen Chen, Shuying Dong, Gaofeng Zhang, Jia Li, Xilan Yang, Yan Li
• Journal: International journal of clinical and experimental pathology (Int J Clin Exp Pathol) Vol. 8 Issue 5 Pg. 4581-7 ( 2015) ISSN: 1936-2625 [Electronic] United States
• PMID: 26191148 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Lipopolysaccharides
• Pyrazines
• RNA, Messenger
• lipopolysaccharide, Escherichia coli O111 B4
• Peroxidase
• ROCK2 protein, rat
• rho-Associated Kinases
• rhoA GTP-Binding Protein
• tetramethylpyrazine

Topics

• Acute Lung Injury (chemically induced, enzymology, genetics, pathology, physiopathology, prevention & control)
• Animals
• Anti-Inflammatory Agents (administration & dosage, pharmacology)
• Bronchoalveolar Lavage Fluid (chemistry, cytology)
• Cytoprotection
• Down-Regulation
• Injections, Intraperitoneal
• Lipopolysaccharides
• Lung (drug effects, enzymology, pathology, physiopathology)
• Male
• Neutrophil Infiltration (drug effects)
• Neutrophils (drug effects, enzymology)
• Peroxidase (metabolism)
• Pyrazines (administration & dosage, pharmacology)
• RNA, Messenger (metabolism)
• Rats, Wistar
• Respiratory Rate (drug effects)
• Signal Transduction (drug effects)
• rho-Associated Kinases (genetics, metabolism)
• rhoA GTP-Binding Protein (metabolism)