Study on baritinib improving pulmonary endothelial barrier injury in acute lung injury mice by regulating the JAK2/STAT3 pathway
10.13699/j.cnki.1001-6821.2024.16.013
- VernacularTitle:巴瑞替尼通过JAK2/STAT3通路改善急性肺损伤小鼠肺内皮屏障损伤的研究
- Author:
Lin WANG
1
;
Jun-Fang CHEN
;
Bao-Liang ZHAO
;
Xue-Li WANG
Author Information
1. 商丘医学高等专科学校临床医学院,河南商丘 476000
- Keywords:
baretinib;
Janus kinase 2;
signal transducer and activator of transcription 3;
acute lung injury;
endothelial barrier;
lipopolysaccharide
- From:
The Chinese Journal of Clinical Pharmacology
2024;40(16):2363-2367
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the effect of barretinib on mice with acute lung injury(ALI)by regulating the Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)pathway.Methods The male C57BL/6 mice were randomly divided into control group,model group and experimental-L,-M-H groups.Except for the control group,the other four groups were constructed ALI models by intraperitoneal injection of lipopolysaccharide.The control and model groups were given equal volume 0.9％NaCl by gavage.The experimental-H,-M,-L groups were administered with 1.00,0.50 and 0.25 mg·mL-1 barretinib solution 200 μL by gavage.Five groups were treated for 48 hours with once every 12 hours.The levels of inflammatory cytokine in bronchoalveolar lavage fluid were measured by enzyme linked immunosorbent assay.The expression levels of Occludin,JAK2 and STAT3 in mouse lung tissue were detected by Western blot.Results The levels of tumor necrosis factor-α in bronchoalveolar lavage fluid for experimental-M,-H groups,model group and control group were(228.48±25.41),(198.53±23.11),(317.32±32.85)and(48.93±2.59)ng·L-1;the levels of interleukin-6 were(118.81±14.85),(98.58±13.82),(172.23±25.94)and(49.47±3.06)ng·L-1;the relative expression levels of Occludin were 0.48±0.13,0.49±0.11,0.28±0.09 and 0.69±0.21;the phospho-JAK2/JAK2 ratios were 0.51±0.13,0.32±0.09,0.75±0.21 and 0.16±0.05;the phospho-STAT3/STAT3 ratios were 0.43±0.11,0.27±0.08,0.78±0.21 and 0.17±0.05,respectively.The differences of above indicators were statistically significant between the experimental-M,-H groups,control group and model group(all P＜0.05).Conclusion Barretinib can reduce the lung inflammatory response and improves the level of tight junction protein in lung tissue to protect ALI mice by inhibiting the JAK2/STAT3 signaling pathway.
