Vagal Efferent Fiber Stimulation Ameliorates Pulmonary Microvascular Endothelial Cell Injury by Downregulating Inflammat
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Vagal Efferent Fiber Stimulation Ameliorates Pulmonary Microvascular Endothelial Cell Injury by Downregulating Inflammatory Responses Chao Chen,1 Ying Zhang,1 Zhaohui Du,1,2 Min Zhang,1 Li Niu,1 Yanlin Wang,1 and Jianguo Li1
Abstract—Electrical stimulation of the vagus nerve may have positive effects on many inflammatory diseases. This study determined the beneficial effects of vagus nerve stimulation and the mechanisms by which it attenuates lipopolysaccharide (LPS)-induced acute lung injury (ALI). Rats were intraperitoneally injected with 10 mg/kg LPS to induce ALI. The results showed that vagus nerve stimulation could improve lung injury, as evidenced by remarkable reductions in lung edema (wet-to-dry weight ratio), neutrophil infiltration (myeloperoxidase activity), and pulmonary permeability [total number of cells and protein concentrations in bronchoalveolar lavage fluid (BALF)]. In addition, vagus nerve stimulation not only decreased the expressions of Src-suppressed C kinase substrate and E-selectin proteins in lung tissue but also effectively attenuated the concentrations of the proinflammatory cytokines tumor necrosis factor-α, interleukin-1β, and interleukin-6 in BALF. These suggest that vagus nerve stimulation is a suitable treatment for LPS-induced ALI and indicate that it helps ameliorate pulmonary microvascular endothelial cell injury by downregulating inflammatory responses. KEY WORDS: vagal stimulation; lipopolysaccharide; acute lung injury; Src-suppressed C kinase substrate; E-selectin.
INTRODUCTION Acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS), are the most common complications of sepsis. Despite extensive investigations on new strategies for treatment, the morbidity and mortality of sepsis-induced ALI in critically ill patients remain unacceptably high [1]. The pathophysiological mechanism of ALI involves alveolar damage caused by the proliferation of inflammation, increased endothelial cell spacing, increased capillary permeability, alveolar edema, inflammatory cells in the circulation and fluid extravasation into the alveoli, and hyaline membrane formation [2]. 1
Department of Anesthesia, Critical Care Medicine & Emergency Medicine Center, Zhongnan Hospital, Wuhan University, Wuhan, 430071, Hubei Province, People’s Republic of China 2 To whom correspondence should be addressed at Department of Anesthesia, Critical Care Medicine & Emergency Medicine Center, Zhongnan Hospital, Wuhan University, Wuhan, 430071, Hubei Province, People’s Republic of China. E-mail: [email protected]
Vascular endothelial cells are not only passive target cells in inflammatory responses but also effector cells [3], and changes in their morphology and functions are crucial to the evolution of sepsis [4]. Lipopolysaccharide (LPS), the major constituent of the outer cell wall of Gram-negative bacteria, exerts its toxic effects on the lungs through direct injury to endothelial cells and indirect activation of neutrophils and macrophages, thereby releasing proinflammatory cytokines, such as tu
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