Ghrelin Protects Lipopolysaccharide-Induced Acute Lung Injury Rats against Pulmonary Vascular Dysfunction by Inhibiting Inflammation

Guang Li,Chen-Liang Zhou,Wen-Fang Xia,Di Zhang,Hui-Qing Lin

doi:10.1155/2021/6643398

Abstract

Objective. To determine the effect and mechanism of the anti-inflammatory agent ghrelin on pulmonary vascular dysfunction (PVD) in lipopolysaccharide- (LPS-) induced acute lung injury (ALI) rat models. Methods. Thirty-two adult male Sprague Dawley rats (n = 16/group) were randomly divided into ghrelin and saline groups, wherein ghrelin (10 nmol/kg) or saline was subcutaneously administered. After 30 min, eight rats from each group were randomly selected, and LPS (5 mg/kg) or saline was administered by intratracheal instillation to induce ALI. Four hours after establishing the ALI rat model, the mean pulmonary arterial pressure (mPAP), mean right ventricular systolic pressure (RVSP), levels of proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the bronchoalveolar lavage fluid (BALF), BALF cell count, wet-to-dry (W/D) lung weight ratios, and myeloperoxidase (MPO) activity in lung tissue for all four groups (ghrelin, ghrelin + ALI, saline, and saline + ALI) were measured. Immunohistochemical staining to detect alpha-smooth muscle actin (α-SMA) and proliferating cell nuclear antigen (PCNA) expression was performed to assess the intrapulmonary arterial wall thickness and the proliferation of smooth muscle cells, respectively. Results. The ghrelin-pretreated ALI rats showed lower mPAP, RVSP, PCNA expression, MPO activity, W/D lung weight ratio, TNF-α and IL-6 levels, and BALF cell count than the saline-pretreated ALI rats, but ghrelin had no effect on the intrapulmonary arterial wall thickness of ALI rats. Conclusion. Our results confirmed the association between inflammation and PVD in ALI and suggested that the suppression of inflammation by ghrelin pretreatment could protect LPS-induced ALI rats against PVD.

Highlights

Acute lung injury (ALI) and its most severe form, acute respiratory distress syndrome (ARDS), are characterized by acute-onset hypoxia, which leads to diffuse alveolar damage, increased pulmonary vascular permeability, noncardiogenic pulmonary edema, and poor lung compliance [1]
Right ventricular dysfunction as well as persistent and severe hypoxemia due to pulmonary vascular dysfunction (PVD), which is common in ALI [3, 4], increases the morbidity and mortality rates of ALI [5]. erefore, there is an urgent need to better understand PVD in order to clarify the etiology and pathogenesis of ALI. e reported pathophysiological changes occurring due to PVD in ALI include endothelial dysfunction, pulmonary vascular occlusion, increased vascular tone, extrinsic vessel occlusion, and vascular remodeling [6]. e excessive secretion of chemokines and cytokines during an inflammatory response in ALI reportedly results in PVD [7, 8]. us, this study aimed to determine the association between inflammation and PVD in ALI through the use of the anti-inflammatory agent ghrelin
Fewer and occasionally visible proliferating cell nuclear antigen (PCNA)+ cells were observed in the vascular adventitia, medial membrane, intima, and neointima for the ghrelin + ALI group, compared with the ALI group. ere was no significant difference in the thickness of the intrapulmonary intima-media arterial wall among all four groups (Figure 2(b))

Summary

Introduction

Acute lung injury (ALI) and its most severe form, acute respiratory distress syndrome (ARDS), are characterized by acute-onset hypoxia, which leads to diffuse alveolar damage, increased pulmonary vascular permeability, noncardiogenic pulmonary edema, and poor lung compliance [1]. Sepsis and lipopolysaccharide (LPS) are well-known factors that can induce ALI due to their proinflammatory effects. Sepsis-induced ALI has a high mortality rate of 25–50% [2]. At present, there is no effective therapy for ALI/ ARDS due to the lack of understanding of the disease etiology, despite significant efforts in investigating the mechanisms underlying the pathogenesis, treatment, and prevention of this disease. Right ventricular dysfunction as well as persistent and severe hypoxemia due to pulmonary vascular dysfunction (PVD), which is common in ALI [3, 4], increases the morbidity and mortality rates of ALI [5]. Erefore, there is an urgent need to better understand PVD in order to clarify the etiology and pathogenesis of ALI. Right ventricular dysfunction as well as persistent and severe hypoxemia due to pulmonary vascular dysfunction (PVD), which is common in ALI [3, 4], increases the morbidity and mortality rates of ALI [5]. erefore, there is an urgent need to better understand PVD in order to clarify the etiology and pathogenesis of ALI. e reported pathophysiological changes occurring due to PVD in ALI include endothelial dysfunction, pulmonary vascular occlusion, increased vascular tone, extrinsic vessel occlusion, and vascular remodeling [6]. e excessive secretion of chemokines and cytokines during an inflammatory response in ALI reportedly results in PVD [7, 8]. us, this study aimed to determine the association between inflammation and PVD in ALI through the use of the anti-inflammatory agent ghrelin.

Methods

Results

Conclusion