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Protective Effect of Dexmedetomidine on Acute Lung Injury via the Upregulation of Tumour Necrosis Factor-α-Induced Protein-8-like 2 in Septic Mice

  • Qian Kong
  • Xiaojing Wu
  • Zhen Qiu
  • Qin Huang
  • Zhongyuan XiaEmail author
  • Xuemin SongEmail author
Original Article


The aim of the present study was to investigate whether TIPE2 participates in the protective actions of dexmedetomidine (DEX) in a mouse model of sepsis-induced acute lung injury (ALI). We administered TIPE2 adeno-associated virus (AAV-TIPE2) intratracheally into the lungs of mice. Control mice were infected with an adeno-associated virus expressing no transgene. Three weeks later, an animal model of caecal ligation-perforation (CLP)-induced sepsis was established. DEX was administered intravenously 30 min after CLP. Twenty-four hours after sepsis, lung injury was assayed by lung histology, the ratio of polymorphonuclear leukocytes (PMNs) to total cells in the bronchoalveolar lavage fluid (BALF), myeloperoxidase (MPO) activity, BALF protein content and the lung wet-to-dry (W/D) weight ratio. Proinflammatory factor levels in the BALF of mice were measured. The protein expression levels in lung tissues were analysed by Western blotting. The results showed that DEX treatment markedly mitigated sepsis-induced lung injury, which was characterized by the deterioration of histopathology, histologic scores, the W/D weight ratio and total protein levels in the BALF. Moreover, DEX markedly attenuated sepsis-induced lung inflammation, as evidenced by the decrease in the number of PMNs in the BALF, lung MPO activity and proinflammatory cytokines in the BALF. In addition, DEX dramatically prevented sepsis-induced pulmonary cell apoptosis in mice, as reflected by decreases in the number of TUNEL-positive cells, the protein expression of cleaved caspase-9 and cleaved caspase 3 and the Bax/Bcl-2 ratio. In addition, evaluation of protein expression showed that DEX blocked sepsis-activated JNK phosphorylation and NF-κB p65 nuclear translocation. Similar results were also observed in the TIPE2 overexpression group. Our study demonstrated that DEX inhibits acute inflammation and apoptosis in a murine model of sepsis-stimulated ALI via the upregulation of TIPE2 and the suppression of the activation of the NF-κB and JNK signalling pathways.


acute lung injury TIPE2 dexmedetomidine apoptosis inflammation 



acute lung injury


acute respiratory distress syndrome


caecal ligation-perforation


bronchoalveolar lavage fluid


enzyme-linked immunosorbent assay




phosphate-buffered saline


polymorphonuclear neutrophils


deoxynucleotidyl transferase dUTP nick end labelling




tumour necrosis factor-α-induced protein 8-like 2




Bcl-2-associated X


B cell lymphoma 2



This study was supported by the National Natural Science Foundation of China (no. 81571941 and no. 81671948).

Compliance with Ethical Standards

Ethical approval was provided by the Medical Ethics Committee of Renmin Hospital of Wuhan University. All surgical procedures were performed in accordance with international and institutional guidelines for animal care.

Conflict of Interest

The authors declare that they have no conflict of interests.


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© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  1. 1.Department of AnesthesiologyRenmin Hospital of Wuhan UniversityWuhanChina
  2. 2.Department of Anesthesiology and Critical Care MedicineZhongnan Hospital of Wuhan UniversityWuhanChina

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