title: 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.affiliation: Department of Pathophysiology, Bengbu Medical College Bengbu 233030, Anhui Province, PR China.
authors.forename: Shidi
authors.initials: S
authors.lastname: Zhao
authors.affiliation: The First Affiliated Hospital of Bengbu Medical College Bengbu 233030, Anhui Province, PR China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pathophysiology, Bengbu Medical College Bengbu 233030, Anhui Province, PR China.
authors.forename: Qianfen
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Pathophysiology, Bengbu Medical College Bengbu 233030, Anhui Province, PR China.
authors.forename: Shuying
authors.initials: S
authors.lastname: Dong
authors.affiliation: Department of Pathophysiology, Bengbu Medical College Bengbu 233030, Anhui Province, PR China.
authors.forename: Gaofeng
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Pathophysiology, Bengbu Medical College Bengbu 233030, Anhui Province, PR China.
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pathophysiology, Bengbu Medical College Bengbu 233030, Anhui Province, PR China.
authors.forename: Xilan
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Pathophysiology, Bengbu Medical College Bengbu 233030, Anhui Province, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D019610:Cytoprotection; D015536:Down-Regulation; D007274:Injections, Intraperitoneal; D008070:Lipopolysaccharides; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D008297:Male; D020556:Neutrophil Infiltration / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology; D009195:Peroxidase / Q000378:metabolism; D011719:Pyrazines / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D017208:Rats, Wistar; D056152:Respiratory Rate / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D054460:rho-Associated Kinases / Q000235:genetics / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D011719:Pyrazines; D012333:RNA, Messenger; C440499:lipopolysaccharide, Escherichia coli O111 B4; D009195:Peroxidase; C580818:ROCK2 protein, rat; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein; C017953:tetramethylpyrazine
keywords: Acute lung injury (ALI); animal model; lipopolysaccharide (LPS); rat; tetramethylpyrazine (TMP); two-hit hypothesis