Related Experiment Video
Updated: Jul 16, 2026
Pressure Controlled Ventilation to Induce Acute Lung Injury in Mice
Published on: May 5, 2011
[Activation of p38 mitogen-activated protein kinase pathway in ventilator-induced lung injury in rat]
Dan Feng1, Shang-long Yao, You Shang
1Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China.
Objective:
To study the activation of p38 mitogen-activated protein kinase (MAPK) and the expression of inflammatory cytokines in ventilator-induced lung injury (VILI) in rat.
Methods:
Thirty healthy male SD rats were randomly divided into three group (A, B, C group, n=10 per group). Mechanical ventilation was instituted in all the groups. A group: tidal volume (V(T))=8 ml/kg, respiratory rate (RR)=80/min; B group: V(T)=20 ml/kg, RR=80/min; C group: V(T)=40 ml/kg, RR=80/min. The time of ventilation for all the groups was two hours. Rats were sacrificed after experiment was finished. The bronchial lavage liquid and lung tissue were collected and stored with routine methods. The pathological changes in lung tissue were examined with optical microscope. The expression of p38 and phos-p38 (p-p38) were measured by Western blotting in lung tissues. The expression of intercellular adhesion molecular-1 (ICAM-1) was detected by reverse transcriptase-polymerase chain reaction (RT-PCR). The contents of total protein, white blood cells (WBC), myeloperoxidase (MPO), macrophage inflammatory protein-2 (MIP-2) and tumor necrosis factor-alpha (TNF-alpha) were also determined.
Results:
Compared with A group, total protein, WBC, MPO, MIP-2, TNF-alpha, ICAM-1 and p-p38 were significantly increased in B group and C group (all P<0.01). Compared with B group, the above indexes were also significantly increased in C group (P<0.05 or P<0.01).
Conclusion:
Large V(T) mechanical ventilation can significantly activate the p-p38 and inflammatory cytokines, which may play an important role in VILI.
Insights
High tidal volume mechanical ventilation significantly increases p38 mitogen-activated protein kinase (MAPK) activation and inflammatory cytokines, contributing to ventilator-induced lung injury (VILI). This study highlights the role of these factors in VILI development.
Area of Science:
- Pulmonary Medicine
- Cellular Biology
- Biochemistry
Context:
- Mechanical ventilation is crucial for respiratory support but can induce lung injury.
- Ventilator-induced lung injury (VILI) is a significant clinical complication.
- The role of p38 MAPK and inflammatory cytokines in VILI pathogenesis requires further elucidation.
Purpose:
- To investigate the activation of p38 MAPK and the expression of inflammatory cytokines in a rat model of VILI.
- To determine the impact of varying tidal volumes on these molecular markers.
Summary:
- Rats subjected to mechanical ventilation with higher tidal volumes (20 ml/kg and 40 ml/kg) exhibited significantly increased levels of p-p38, ICAM-1, TNF-alpha, MIP-2, WBC, MPO, and total protein compared to a low tidal volume group (8 ml/kg).
- A dose-dependent increase in these inflammatory markers was observed with increasing tidal volumes.
- Pathological changes in lung tissue correlated with the elevated molecular markers.
Impact:
- Findings suggest that high tidal volume ventilation activates p38 MAPK and promotes the release of inflammatory cytokines.
- These molecular events are implicated as key contributors to the development of VILI.
- This research provides insights into potential therapeutic targets for mitigating VILI.
