ObjectiveTo investigate the role of mammalian STE20-like kinase 1 (MST1) in sepsis-induced acute lung injury (ALI) and its molecular mechanisms in regulating the nuclear factor-erythroid 2 related factor 2 (Nrf2)/heme oxygenase 1(HO-1) antioxidant signaling pathway. MethodsA murine sepsis-induced ALI model was established by intraperitoneal injection of lipopolysaccharide (LPS, 5 mg/kg). Lung injury was assessed by hematoxylin-eosin (HE) staining, lung injury scoring, and bronchoalveolar lavage fluid (BALF) analysis. Mst1 knockout mice and RAW264.7 macrophages were used. Related proteins and inflammatory factors were detected by Western blot, qRT-PCR, immunofluorescence, and ELISA. The regulatory relationship of the Mst1-Nrf2/HO-1 signaling axis was verified using siRNA knockdown and overexpression techniques combined with Nrf2 inhibitor and activator treatments. ResultsAfter LPS treatment, mouse lung tissues showed typical ALI pathological changes, and Mst1 protein expression was upregulated in a time-dependent manner. Mst1 deficiency significantly alleviated lung injury and reduced protein concentration and inflammatory cell counts in BALF. In vitro experiments showed that Mst1 knockdown in RAW264.7 macrophages inhibited LPS-induced secretion of tumor necrosis factor-α, interleukin-6, and interleukin-1β. Mechanistic studies revealed that Mst1 promoted oxidative stress and inflammatory responses by inhibiting Nrf2 nuclear translocation and HO-1 expression. Nrf2 inhibitor partially reversed the protective effects of Mst1 knockdown, while the Nrf2 activator tBHQ significantly improved lung injury. ConclusionsMst1 promotes the development of sepsis-induced ALI through negative regulation of the Nrf2/HO-1 antioxidant signaling pathway. Mst1 may serve as a potential therapeutic target for sepsis-induced ALI.
Objectives To investigate the pathogenic characteristics and the possible relationship between pathogen and respiratory function in patients with acute exacerbations of COPD (AECOPD).Methods Sixty-four patients with AECOPD were investigated with lung function test，quantitative and qualitative sputum bacteria culture，drug sensitive test，and Mycoplasma pneumoniae and Chlamydia pneumoniae specific antibodies test.The patients were divided into three groups according to FEV1%pred，50%≤FEV1lt;80%pred for the Group One，30%pred≤FEV1lt;50%pred for the Group Two，and FEV1lt;30%pred for the Group Three.Meanwhile according to the result of sputum culture，infective bacteria were divided into four kinds： Gram-positive cocci for kind A，Gram-negtive germ except kind C for kind B，Acinetobacter，Enterobacter and Pseudomonas spp for kind C，and negative result for kind D.Results ⑴Of 64 patients who were conducted quantitative sputum culture，germs isolated were mostly Streptococcus pneumoniae，Enterobacter，Moraxella Catarrhalis，and Pseudomonas.Of 38 patients who were conducted qualitative sputum culture，most of them were found mixed infection，and germs isolated were mostly Streptococcus pneumoniae，Staphylococcus epidermidis，Acinetobacter and Enterobacter.⑵Both quantitative and qualitative sputum culture revealed that Most of Group One patients were not infected by bacteria，and the Group Three patients were mainly by resistant kind A and kind C bacteria (Plt;0.01 and 0.05 respectively).⑶The infection of Mycoplasma pneumoniae or Chlamydia pneumoniae was identified in 29.4% of the cases.Conclusions There is a close correlation between the degree of functional damage and the infected bacterial strains for patients with AECOPD，the more chance of bacteria infection such as S pneumoniae，Acinetobacter，Enterobacter and Pseudomonas，the more damage of lung function.