Abstract: Objective To evaluate the effects of different doses of leptin on mucin MUC5AC in rats with ventilator‑induced lung injury (VILI). Methods According to the random number table method, forty eight healthy adult male SD rats (aged 6 to 8 weeks) were divided into four groups (n=12): a sham‑operated group (group A, with spontaneous breathing after tracheal incision), a VILI group (group B), a small‑dose leptin group (group C, 10 μg/kg), and a large‑dose group (group D, 50 μg/kg). Rats in groups B, C and D were mechanically ventilated to establish a model of VILI: tidal volume 20 ml/kg, ventilation frequency 80 bpm, inspiration‑expiration ratio: 1∶1, FiO2 21%, and positive‑end expiratory pressure (PEEP) 0 mmHg (1 mmHg=0.133 kPa), ventilation duration 4 h. Groups C and D were intraperitoneally injected with leptin, while groups A and B were intraperitoneally injected with the same volume of normal saline. Ventilation started immediately after injection. Blood samples were collected from the femoral artery immediately before tracheal intubation (T1) and after the end of ventilation (T2). After modeling, bronchoalveolar lavage fluid (BALF) was collected to determine the amounts of tumor necrosis factor‑α (TNF‑α), interleukin‑6 (IL‑6), and IL‑1β, and the number of neutrophils was counted. The lung specimens were obtained to determine the wet/dry weight (W/D) ratio. The pathological changes in lung tissues were observed and scored. The morphopathogical changes in the lungs were observed by hematoxylin‑eosin (HE) staining. The expression of mucin MUC5AC was measured by immunohistochemical assay. The levels of nuclear factor‑κB (NF‑κB) p65 and mucin MUC5AC in lung tissue were detected. Results Groups C and D presented relieved pathological changes compared with group B, where declined pathological changes were found in group D compared with group C. Compared with T1, PaO2 decreased in group B, group C and group D at T2 (P<0.01). Compared with group A, PaO2 in group B, group C and group D decreased at T2 (P<0.01). Compared with group A, W/D, lung injury score and neutrophil count of group B, group C and group D increased (P<0.01). The lung injury score and BALF neutrophil count in group C and D were lower than those in group B (P<0.05). The lung injury score and neutrophil count in group D were significantly lower than those in group C (P<0.05). Compared with group A, TNF‑α, IL‑6 and IL‑1β in BALF of group B, C and D were increased (P<0.01). The contents of TNF‑α, IL‑6 and IL‑1β in BALF in group C and D were lower than those in group B (P<0.05), and those in group D were lower than those in group C (P<0.05). The levels of MUC5AC and NF‑κB p65 in group C and D were lower than those in group B (P<0.05), and those in group D were lower than those in group C (P<0.05). Conclusions Leptin can inhibit the expression of inflammatory factors in rats with VILI, reduce the expression of mucin MUC5AC, and relieve pulmonary injury. More obvious effects can be found after injection with a higher dose (50 μg/kg).
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