Bone Marrow-Derived Mesenchymal Stem Cells Alleviate Posthemorrhagic Shock Mesenteric Lymph-Induced Acute Lung Injury

Abstract

Introduction

Mesenteric lymph is recognized as a conduit in the gut-lung axis. Posthemorrhagic shock mesenteric lymph (PHSML) contains proinflammatory substances and can exacerbate the acute lung injury (ALI) induced by hemorrhagic shock (HS). Mesenchymal stem cells (MSCs) possess anti-inflammatory properties and hold therapeutic potential for ALI. However, the effect and mechanism of MSCs in alleviating PHSML-mediated ALI remains unclear.

Methods

Rat hemorrhage shock model and PHSML infusion model were used to induce ALI. MSCs were administrated intravenously to treat ALI. Pulmonary function of rats was assessed by a Buxco pulmonary function analysis system. Hematoxylin and eosin staining was used for histological analysis. Western blot and quantitative real-time polymerase chain reaction were used to detect the expressions of inflammation-related genes.

Results

Intravenous infusion of bone marrow-derived MSCs (BMSCs) prolonged the survival of HS rats. Both HS and PHSML could cause pulmonary tissue damage, lung edema, and pulmonary dysfunction, which were all alleviated by BMSC treatment. The pulmonary dysfunction indices (inspiratory resistance, functional residual capacity, and mean mid expiratory flow) were significantly improved by BMSC treatment in the two models. C-X-C motif chemokine ligand and inducible nitric oxide synthase, which are important for neutrophil recruitment and infiltration to the injured site, were down-regulated by BMSCs in the lung tissues of rats with HS or PHSML injury. As a neutrophil marker, myeloperoxidase is also decreased by BMSC treatment. These results indicated that BMSCs may reduce neutrophil recruitment and infiltration through inhibiting C-X-C motif chemokine ligand and inducible nitric oxide synthase expressions.

Conclusions

The current findings demonstrate that BMSC therapy can alleviate the ALI induced by PHSML. In mechanism, BMSCs can protect lungs from the inflammatory response mediated by neutrophils. Our study provides novel insight to treat ALI in the gut lymphatics-lung axis.