Resolvin D1 Alleviates Ventilator-Induced Lung Injury in Mice by Activating PPARγ/NF-κB Signaling Pathway

Haifa Xia,Jingxu Wang,Shujun Sun,Lin Chen,Fuquan Wang,Shanglong Yao,Zhipeng Sun,Yiyi Yang

doi:10.1155/2019/6254587

Abstract

As one of the basic treatment modalities in the intensive care unit (ICU), mechanical ventilation can cause or aggravate acute lung injury or ventilator-induced lung injury (VILI). Resolvin D1 (RvD1) is an endogenous polyunsaturated fatty acid derivative with strong anti-inflammatory action. In this study, we explored if RvD1 possesses a protective effect on VILI. Mice were ventilated with high tidal volume (40 mL/kg, HVT) for 4 h and were then intraperitoneally administered RvD1 at the beginning of high tidal volume ventilation and given GW9662 (a PPAR-γ antagonist) intraperitoneally 30 min before ventilation. RvD1 attenuated VILI, as evidenced by improved oxygenation and reduced histological injury, compared with HVT -induced lung injury. Similarly, it could ameliorate neutrophil accumulation and production of proinflammatory cytokines in lung tissue. In contrast, the protective effect of RvD1 on lung tissue could be reversed by GW9662. RvD1 mitigated VILI by activating peroxisome proliferator-activated receptor gamma (PPAR-γ) and inhibiting nuclear factor-kappa B (NF-κB) signaling pathways in mice. In conclusion, RvD1 could reduce the inflammatory response in VILI by activating PPAR-γ and inhibiting NF-κB signaling pathways.

Highlights

Mechanical ventilation (MV), an essential technology in the intensive care unit (ICU), as a life-saving measure, is extensively applied in patients with pulmonary dysfunction or injury
MV can cause and aggravate lung injury, thereby putting patients at risk of ventilator-induced lung injury (VILI), which can lead to increased morbidity and mortality [1,2,3], especially when the therapeutic focus is mainly directed at inflammation inhibition, since VILI is characterized by destruction of the alveolar-capillary barrier and increased permeability, resulting in edema, inflammatory leukocyte infiltration, and bleeding [3, 4]
Animals treated with GW9662 exhibited changes similar to those found in the HVT animals (Figure 2(d)) and their lung injury scores were consistent with the pathohistological changes (Figure 2(e))

Summary

Introduction

Mechanical ventilation (MV), an essential technology in the intensive care unit (ICU), as a life-saving measure, is extensively applied in patients with pulmonary dysfunction or injury. MV can cause and aggravate lung injury, thereby putting patients at risk of ventilator-induced lung injury (VILI), which can lead to increased morbidity and mortality [1,2,3], especially when the therapeutic focus is mainly directed at inflammation inhibition, since VILI is characterized by destruction of the alveolar-capillary barrier and increased permeability, resulting in edema, inflammatory leukocyte infiltration (predominantly neutrophils), and bleeding [3, 4]. Resolvin D1 (RvD1) was stereochemically assigned as 7S, 8R, 17S-trihydroxy-4Z, 9E, 11E, 13Z, 15E, and 19Z-docosahexaenoic acid [11], and previous studies showed that it possessed effective and stereoselective antiinflammatory effects, such as limiting neutrophil infiltration and promoting apoptosis [12]. RvD1 promotes inflammatory resolving mainly by reducing neutrophil infiltration, inhibiting the interaction between neutrophils and platelets, and enhancing restitution of barrier integrity [15].

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Conclusion