| Objective To investigate the effects of shikonin on extracellular signal-regulated kinase/p38 mitogen-activated proteinkinase/nucleotide binding oligomerization domain like receptor protein 3 (ERK/p38/NLRP3) signal pathway and pulmonary vascularpermeability in Streptococcus pneumoniae induced pneumonia mice.Methods The pneumonia model of Streptococcus pneumoniaewas established by dropping 50 L of Streptococcus pneumoniae suspension to the damaged nasal mucosa of BALB/c mice, the modelmice were randomly divided into model group, low, medium and high concentrations of shikonin groups and cefuroxime axetil group, inaddition, the BALB/c mice with 50 L normal saline added into the nasal cavity were taken as the control group, with 10 in each group.Shikonin of 12.5 mg/kg, 25.0 mg/kg and 50.0 mg/kg were given to the low, medium and high concentration groups respectively, in cefuroxime axetil group, 50.0 mg/kg cefuroxime axetil was given, the control group and the model group were given the same amount of normal saline, once a day gavage for 7 days. The mice were killed at 12 hours after the last administration, the ratio of left lung wet to dryweight (w/D) was measured, four mice in each group were randomly selected for 1% Evans Blue 5 mL/kg tail vein injection to detectpulmonary vascular permeability, the expressions of IL-1β and TNF-α in lung tissue were detected by enzyme-linked immunosorbent assay (ELISA), and the relative expressions of ERK, p38, NLRP3 mRNA and protein were detected by real-time fluorescent quantitative PCR (RT-qPCR) and Western blot (WB) respectively.Results Compared with those in the control group, the W/D ratio of lung tissue, pulmonary vascular permeability, expressions of IL-1β and TNF-α, and the expression levels of ERK, p38, NLRP3 mRNA and protein of mice in the model group were significantly higher (P < 0.05); compared with those in the model group, the W/D ratio of lung tissue[(4.49±0.27)% vs.(3.02±0.15)%], pulmonary vascular permeability[(0.091±0.009) g/mg vs.(0.034±0.004) g/mg], expressions of IL-1β [(567.29±14.65)pg/mL vs.(102.46±6.73)pg/mL] and TNF-α[(417.16±12.89)pg/mL vs.(83.59±6.28)pg/mL], and the expression levels ofERK, p38, NLRP3 mRNA and protein of mice in the low, medium and high concentration of shikonin groups decreased in turn (P< 0.05), and those in the the high concentration of shikonin group was lower than those in the cefuroxime axetil group (P<0.05).Conclu? sion Shikonin can reduce lung injury, inflammation and pulmonary vascular permeability in streptococcus pneumoniae mice, whichmay be related to the inhibition of ERK/p38/NLRP3 signaling pathway. |
