scholarly journals Protective Effect of Artesunate on LPS-induced Acute Lung Injury by Anti-oxidant Through AKT/PI3K Pathway

Author(s):  
Guo-quan WANG ◽  
Xu CHAO ◽  
Sha LI ◽  
Lin-zhong YU ◽  
En-hu ZHANG
2017 ◽  
Vol 37 (6) ◽  
pp. 626-635 ◽  
Author(s):  
P Geng ◽  
T Ma ◽  
J Xing ◽  
L Jiang ◽  
H Sun ◽  
...  

Acute lung injury (ALI) is a major outcome of exposure to high levels of hydrogen sulfide (H2S). Dexamethasone (DXM) has been used to treat ALI. However, the mechanisms involved in H2S-induced ALI and the protective mechanisms of DXM in treating ALI are still nebulous. To explore the mechanisms involved, we evaluated the role of claudin-5 in the protective effect of DXM against H2S-induced ALI. Sprague-Dawley rats were exposed to H2S to establish the ALI model. In parallel with the animal model, a cell model was also established by incubating human umbilical vein endothelial cells (HUVECs) with NaHS. Lung hematoxylin–eosin staining, electron microscope assay, and wet/dry ratio were used to identify whether the ALI was successfully induced by H2S, and changes in claudin-5 expression were detected in both rats and HUVECs. Our results revealed that claudin-5 was markedly decreased after H2S exposure and that DXM significantly attenuated the H2S-induced downregulation of claudin-5 in both rats and HUVECs. In the animal experiment, p-Akt and p-FoxO1 presented a similar tendency as claudin-5, but their levels decreased 6 h prior to the levels of claudin-5. In a further investigation, the DXM-induced protective effect on ALI and rescue effect on downregulation of claudin-5 were both blocked by LY294002. The current study demonstrated that claudin-5 was involved in the development of H2S-induced ALI and that DXM exerted protective effects through increasing claudin-5 expression by activating the phosphatidylinositol 3-kinase pathway. Therefore, claudin-5 might represent a novel pharmacological target for treating ALI induced by H2S and other hazardous gases.


2021 ◽  
Vol 49 (2) ◽  
pp. 030006052098635
Author(s):  
Qi Gao ◽  
Ningqing Chang ◽  
Donglian Liu

Objectives To investigate the mechanisms underlying the protective effect of sufentanil against acute lung injury (ALI). Material and Methods Rats were administered lipopolysaccharide (LPS) by endotracheal instillation to establish a model of ALI. LPS was used to stimulate BEAS-2B cells. The targets and promoter activities of IκB were assessed using a luciferase reporter assay. Apoptosis of BEAS-2B cells was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling. Results Sufentanil treatment markedly reduced pathological changes in lung tissue, pulmonary edema and secretion of inflammatory factors associated with ALI in vivo and in vitro. In addition, sufentanil suppressed apoptosis induced by LPS and activated NF-κB both in vivo and in vitro. Furthermore, upregulation of high mobility group box protein 1 (HMGB1) protein levels and downregulation of miR-129-5p levels were observed in vivo and in vitro following sufentanil treatment. miR-129-5p targeted the 3ʹ untranslated region and its inhibition decreased promoter activities of IκB-α. miR-129-5p inhibition significantly weakened the protective effect of sufentanil on LPS-treated BEAS-2B cells. Conclusion Sufentanil regulated the miR-129-5p/HMGB1 axis to enhance IκB-α expression, suggesting that sufentanil represents a candidate drug for ALI protection and providing avenues for clinical treatment.


2014 ◽  
Vol 239 (12) ◽  
pp. 1653-1662 ◽  
Author(s):  
Lian Wang ◽  
Jinming Chen ◽  
Bo Wang ◽  
Dingqian Wu ◽  
Hao Li ◽  
...  

2015 ◽  
Vol 25 (1) ◽  
pp. 55-64 ◽  
Author(s):  
Tong Chen ◽  
Yi Mou ◽  
Jiani Tan ◽  
Linlin Wei ◽  
Yixue Qiao ◽  
...  

2020 ◽  
Vol 80 ◽  
pp. 106174 ◽  
Author(s):  
Yin Xinqiang ◽  
Chen Quan ◽  
Jing Yuanyuan ◽  
Xu Hanmei

2019 ◽  
Vol 39 (6) ◽  
Author(s):  
Shuiqiao Fu ◽  
Weina Lu ◽  
Wenqiao Yu ◽  
Jun Hu

Abstract Background: To study the protective effect of Cordyceps sinensis extract (Dong Chong Xia Cao in Chinese [DCXC]) on experimental acute lung injury (ALI) mice. Methods and results: ALI model was induced by intratracheal-instilled lipopolysaccharide (LPS, 2.4 mg/kg) in BALB/c male mice. The mice were administrated DCXC (ig, 10, 30, 60 mg/kg) in 4 and 8 h after receiving LPS. Histopathological section, wet/dry lung weight ratio and myeloperoxidase activity were detected. Bronchoalveolar lavage fluid (BALF) was collected for cell count, the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and nitric oxide (NO) in BALF was detected by ELISA, the protein and mRNA expression of nuclear factor-κB p65 (NF-κB p65), inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) in lung tissue was detected by Western blot and RT-PCR. The result showed that DCXC could reduce the degree of histopathological injury, wet/dry weight ratio (W/D ratio) and myeloperoxidase activity (P<0.05) with a dose-dependent manner. The increased number of total cells, neutrophils and macrophages in BALF were significantly inhibited by DCXC treatment (P<0.05). The increased levels of TNF-α, IL-1β, IL-6 and NO in BALF after LPS administration was significantly reduced by DCXC (P<0.05). In addition, the increased protein and mRNA levels of iNOS, COX-2 and NF-κB p65 DNA binding ability in LPS group were dose-dependently reduced by DCXC treatment (P<0.05). Conclusion: DCXC could play an anti-inflammatory and antioxidant effect on LPS-induced ALI through inhibiting NF-κB p65 phosphorylation, and the expression of COX-2 and iNOS in lung. The result showed that DCXC has a potential protective effect on the ALI.


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