Tumor necrosis factor α‑induced protein 8‑like 2 contributes to penehyclidine hydrochloride pretreatment against lipopolysaccharide‑induced acute lung injury in a mouse model

Yuan,Min; Jing,Guoqing; Kong,Qian; Ming,Tingqian; Song,Xuemin; Wu,Xiaojing

doi:10.3892/mmr.2021.12390

Tumor necrosis factor α‑induced protein 8‑like 2 contributes to penehyclidine hydrochloride pretreatment against lipopolysaccharide‑induced acute lung injury in a mouse model

Authors:
- Min Yuan
- Guoqing Jing
- Qian Kong
- Tingqian Ming
- Xuemin Song
- Xiaojing Wu
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Affiliations: Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China, Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China, Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
Published online on: August 31, 2021 https://doi.org/10.3892/mmr.2021.12390
Article Number: 750

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Abstract

The aim of the present study was to investigate the effect of penehyclidine hydrochloride (PHC) pretreatment on mice with lipopolysaccharide (LPS)‑induced acute lung injury (ALI) and its possible underlying mechanisms. Mice were randomly separated into six groups: i) Sham group; ii) LPS group; iii) LPS + PHC group; iv) tumor necrosis factor a‑induced protein 8‑like protein 2 (TIPE2) group; v) LPS + TIPE2 group; and vi) LPS + TIPE2 + PHC group. The ALI model was induced using LPS through intratracheal injection. The mice received adenovirus gene to induce the overexpression of TIPE2. After mice were sacrificed, lung injury indices were assessed, and arterial blood, bronchoalveolar lavage fluid and lung tissues were collected for subsequent assays. Expression levels of related proteins were detected by using western blotting. It was found that compared with the sham group, the mice treated with LPS showed increased lung injury and dysfunctions of gas exchange. However, these trends were significantly ameliorated in the LPS + PHC group. Evaluation of protein expression in lung tissues showed that the increased expression of nuclear NF‑κB p65 and p‑c‑Jun N‑terminal kinase (JNK) induced by LPS were suppressed in the LPS + PHC group and the expression of TIPE2 was increased. The mice that received adenovirus gene to induce TIPE2 overexpression could also showed protective effects compared with the mice in the LPS group. However, the expression of TIPE2 decreased rather than increased in LPS group. In the mice pretreated with PHC, the expression of TIPE2 increased in mice with LPS‑induced ALI. To conclude, PHC pretreatment could inhibit the occurrence of inflammation and apoptosis in LPS‑induced ALI. This process may be related to the activation of TIPE2 and the inhibition of NF‑κB and JNK signaling pathway in the lungs of mice.

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