| Objective: Inflammatory mediators play a very important role in the pathogenesis ofacute lung injury (ALI), and transcription factors could regulate the gene expression of a lot of mediators and cytokines. We studied the mechanisms of the inflammatory signal transduction in the model of lipopolysaccharide (LPS)-induced ALI in Sprague-Dawley (S-D) rats by injected intrapritoneally in vivo, and the effects of ambroxol (AMB) and dexamethasone (DEX) to regulate the inflammatory signalling. The aims of this study were to explain: (1) the relationship between nuclear factor-kappa B (NF-kB) activation and LPS-induced ALI; (2) the effects of AMB to regulate the signaling of NF-kB activation; (3) the effects of DEX to regulate the signaling of NF-kB activation; (4) the relationship between the inhibitory effects of AMB and its dosage; (5) the effects of inhibiting the activation of NF-kB, inhibitor of NF-kB (IkB) and c-Jun-N terminal kinase (JNK) on inflammatory mediator expression; (6) whether it had synergistic action or not if AMB and DEX were used together in the treatment.Methods:1. Classification: Male S-D rats, body weight 237 ± 34g, were used in all experiments.There was no evidence that any of the rats used in these experiments was infected.They were divided into two parts. The first part was divided into control group, LPSgroup, AMB group, DEX group, LPS+AMB (5mg/kg) group, LPS+AMB (lOmg/kg) group, LPS+AMB (20mg/kg) group, LPS+DEX (l.0mg/kg) group, and LPS+AMB (10mg/kg)+DEX (l.0mg/kg) group. Each group was further divided into 3 subgroups at 1,2, and 4 hours. There were 4-5 rats in each subgroup. The second part for pathomorphology, 3 rats in each subgroup, was divided into groups as above. All the animals were treated with sodium pentathol anesthesia by intraperitoneal injection (I.P.) as 30mg/kg body weight.2. Animal Models: A) control group: 0.5ml saline (sterile pyrogen-free physiologic saline) by I.P., another 0.5ml saline was given by I.P. after lhr; B) LPS group: 0.5ml saline was given lhr before LPS (5mg/kg weighting) by I.P.; C) AMB group: injected with AMB (l0mg/kg) lhr before 0.5ml saline by I.P.; D) DEX group: injected with DEX (l.0mg/kg) lhr before 0.5ml saline by I.P.; E) other groups: received injection of AMB (5, 10, 20mg/kg) , or DEX (l.0mg/kg), or AMB (10mg/kg)+DEX (l.0mg/kg) lhr before LPS (5mg/kg) by I.P. respectively. All the animals were killed with overdose of sodium pentathol at 1, 2, 4hr after LPS treatment respectively, and then the trachea was exposed after 1-cm midline cervical incision. The broncho-alveolar lavage (BAL) was performed through a tracheal cannula with 8ml ice-saline each rat, and the withdrawal rate of broncho-alveolar lavage fluid (BALF) was more than 70%. The animal models for histological study were the same as above, but without BAL. Animals dead were excluded in study.3. Following Parameters were Monitored: A) total cell count, cell differential count, and measurement of total protein, LDH activity, and the concentration of tumor necrosis factor-a (TNF-a), interleukin-lβ (IL-1β), and macrophage inflammatory protein-2(MIP-2) in BALF; B) pathomorphology for lung tissue; C) measurement of NF-kBp65, IkBa, and JNK activation in lung tissue.Results:1. In BALF: A) There were no significant differences between control group, AMBgroup, and DEX group in any parameter (P>0.05). B) In other groups which were challenged by LPS, total number of WBC, percentage of neutrophil , LDH activity, total concentration of protein, concentration of TNF-α, IL-1β, and MIP-2 were significantly higher at 1, 2, 4hr. The total number of macrophage increased significantly, but the percentage of it decreased. There was the most significant differences in LPS groups (P<0.01). All parameters, except the percentage of macrophage, were lowered with AMB and DEX treatment, but there were no significant differences between LPS group and LPS+AMB (5mg/kg) group at any time (P>0.05). There were co-relationship between the effects and AMB dose (r>0.75, P<0.01). There were the most s...
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