The Protective Effect Andmechanismof Fei-Fu-Kang On Lipopolysaccharide-induced Acute Lung Injury

Objective Establish ALI Kunming mice ALI model, investigate the protective effect and potential mechanism of FFK protective effect on LPS induced ALI in mice by estimating pathological changes of lung tissues, protein exudation, edema, inflammatory cell exudation, inflammation cytokine and oxidative stress levels and MAPK signaling pathway protein expression.Methods 60 Kunming male mice were randomly divided into 6 groups:normal control group, LPS model group, pretreatment with FFK group, pretreatment with dexamethasone (DEX) group, treatment with FFK group, and treatment with DEX group. Except the normal control group, other 5 groups were injected with LPS (5 mg/kg) copy the ALI animal model. Pretreatment with FFK group, pretreatment with DEX group were given FFK (30 ml/kg.d), DEX (1 mg/kg.d) preventive medication for 7 days. On the 7th day, the mice were intraperitoneal injection of LPS 1h after FFK and DEX. Then 6h after, the mice were sacrificed. On the first day, treatment with FFK group, treatment with DEX group were given FFK (30 ml/kg.d), DEX (1 mg/kg.d) were given 1h after intraperitoneal injection of LPS. Then the mice were treatment 7 days persistent. On the 7th day, the mice were sacrificed 6h after FFK and DEX gastric lavage. The BALF, serum and lung tissues were collected after sacrificed immediately. HE staining was used to observe the pathological changes of lung tissue, Masson staining was used to observe collagen deposition. Inflammatory cells (the total number of cells, neutropHils, macropHages) were counted in BALF. Protein concentrations were determined by BCA method. Lung tissue wet to dry weight ratios were measured. TNF-αand IL-1β in the serum and BALF were measured by ELISA; lung tissue wet weight to dry weight ratios were measured; myeloperoxidase (MPO) kit was used to measure lung tissue MPO activity in each group. TLR4. MEK1/2, MKK3/6 level, MKK4/7, p38MAPK, ERK1/2, JNK, EIK, c-fos, c-Jun, ATF-2 and those PHospHorylation were evaluated by Western blotting.ResultCompared with the normal control group, the LPS model mice lung tissue could be observed the alveolar wall thickening, neutropHil infiltration, edema, exudation of protein rich edema, micro thrombosis synthesis, hyaline membrane formation; the number of inflammatory cell was increased significantly; protein concentration in BALF was increased significantly; lung wet to dry weight ratio (W/D) was increased significantly; cytokines in BALF and serum were increased significantly; the protein in the cell signaling were activated significantly, while the pretreatment with FFK group, pretreatment with DEX group, treatment with FFK group, and treatment with DEX group could be observed lung structure damage mitigate significantly, the alveolar walls are thickened slightly, neutropHilic exudates reduced, protein rich edema exudation reduced compared with the LPS model group. Masson staining also could be observed in the alveoli collagen deposition also decreased significantly. Compared with the LPS model group, the pretreatment with FFK group, pretreatment with DEX group, treatment with FFK group, and treatment with DEX group number of inflammatory cell was decreased significantly; protein concentration in BALF was decreased significantly; lung wet to dry weight ratio (W/D) was decreased significantly; cytokines in BALF and serum were decreased significantly; the protein in the cell signaling activation were inhibated significantly.Cunclusion Pretreatment and treatment with FFK both could alleviate the lung tissue damage, reduced protein exudation and lung tissue edema, suggested that FFK has a protective effect on mice ALI induced by LPS. The mechanism may be associated with decrease inflammation, reduce oxidative stress, and inhibit MAPK activation in lung tissue.