Abstract
Acute lung injury (ALI) is one of major causes of morbidity and mortality in intensive care. In pathophysiological events of ALI, endothelial surface layer (ESL) injury can result in capillary leakage as the initial event. The “Fusu agent”, a traditional Chinese medicine, can inhibit inflammatory factors, attenuate lung capillary leak as seen in our previous study. This study was aimed to explore the molecular mechanism of Fusu agent treatment with ALI. Consistent with previous studies, we found that Fusu agent has the protective effect on LPS-induced ALI model rats. Further investigation demonstrated that heparanase activation is necessary for the LPS-induced ALI model to aggravate ESL loss. Fusu agent can inhibit heparanase activation and heparan sulfate proteoglycans’ (HSPGs) degradation to mitigate the ESL injury. Furthermore, TNF-α and intercellular adhesion molecule-1 (ICAM-1) were significantly reduced upon Fusu agent pre-treatment to inhibit inflammatory cell influx and neutrophil adhesion in ALI. These findings shed light on the pharmacologic basis for the clinical application of traditional Chinese medicine in treating ALI.
Highlights
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are major causes of death in intensive care
The population-based data suggest that incidence of acute lung injury and ARDS is 1.5–8.3 per 100,000 person-years, likely to double in the decade [1,2,3]
Hydrated heparan sulfate proteoglycans (HSPGs) and heparan sulfate form a substantial endothelial surface layer that acts as the primary barrier to circulating inflammatory cells and large molecules in the systemic circulation
Summary
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are major causes of death in intensive care. The pathophysiologic characters of ALI are systemically complex process, including lung interstitial edema, accumulation and activity of inflammatory leukocytes, increased permeability of endothelial and epithelial barriers [5]. In pathophysiological events of ALI, vascular endothelial cell and endothelial surface layer (ESL) injury is the initial event, the final result is the alveolo-capillary barrier leakage, leading to interstitium and alveoli edema formation [6, 7]. HSPGs are composed of a core protein and one or more heparan sulfate (HS) chains. In these protein families, glypicans (GPC) and syndecans (SDC) contain mostly HS side chains and comprise moderately core proteins. Heparanase (HPA)is an only endo-β-D-glucuronidase capable of cleaving HS side chains
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