Pretreatment with Andrographolide Pills^® Attenuates Lipopolysaccharide‐Induced Pulmonary Microcirculatory Disturbance and Acute Lung Injury in Rats

Abstract

OBJECTIVE: The purpose of this study was to explore the protective effect of AP on LPS-induced PMD and ALI. METHODS: Male SD rats were continuously infused with LPS (5 mg/kg/h) for one hour to induce PMD and ALI. AP was administrated orally one hour before LPS exposure. Arterial blood pressure and HR were monitored. Blood gas analysis, histological observation, cytokines in plasma, leukocyte recruitment, pulmonary oxidative stress, microvessel permeability, edema, and related proteins were evaluated six hours after LPS challenge. RESULTS: Rats receiving LPS exhibited significant alterations, including hypotension, tachycardia, increase in cytokines, neutrophil adhesion and infiltration, oxidative stress, and microvessel hyperpermeability, resulting in pulmonary injury and dysfunction. AP (0.18 g/kg or 1.8 g/kg) improved rat survival rate, and significantly attenuated all aforementioned insults, and inhibited LPS-induced increase in adhesion molecules, up-regulation of Cav-1 and Src kinase and NADPH oxidase subunits (p47(phox) and p67(phox) ) membrane translocation in lung tissue, and preserved JAM-1 and claudin-5. CONCLUSIONS: The results demonstrated the protective effect of AP on LPS-induced PMD and ALI, suggesting the potential of AP as a prophylactic strategy for LPS-induced ALI.