Protective Effect And Its Mechanism Of Agmatine On Lipopolysaccharide-induced Acute Lung Injury In Rats

Acute lung injury(ALI) is characterized by overwhelming lung inflammation and anti-inflammation treatment proposed to be a therapeutic strategy for ALI. Agmatine is a cationic polyamine formed by decarboxylation of L-arginine, and also an endogenous neuromodulator that plays protective roles in diverse central nervous system(CNS)disorders. Consistent with its neuromodulatory and neuroprotective properties, agmatine has been reported to have beneficial effects on depression, anxiety, hypoxic ischemia,Parkinson’s disease, and gastric disorder. This article puts forward that agmatine can regulate the pulmonary inflammation induced by lipopolysaccharide to treat the lung injury.Objective1. To establish a variety of acute lung injury rat model to select a model closer to the clinical;2. To research the protective and mechanism effect of agmatine on lipopolysaccharide induced acute lung injury in rat.Materials and Methods1.There were three methods causing acute lung injury,including intraperitoneal injection of lipopolysaccharide(LPS-IP, 10 mg / kg), instillation of lipopolysaccharide(LPS-IT, 5 mg / kg) and cecal ligation and puncture(CLP). Arterial blood gas was compared between the groups of rats. We adopt hemacytometer, bicinchoninic acid protein assay and Wright Giemsa stain to respectively detect the total number of cells,protein content and category distinction in the bronchoalveolar lavage fluid.In order to evaluate the damage degree of lung tissue, we used hematoxylin- eosin staining method(HE) and wet dry, and then chose the better model of acute lung injury.2. By using the instillation of lipopolysaccharide(LPS-IT, 5 mg / kg) way to cause acute lung injury model in rats, we treat the acute lung injury by using the instillationagmatine(3.5 mg / kg).We detected tissue damage(hematoxylin- eosin staining method),wet/dry weight ratio and myeloperoxidase(MPO) activity of lung tissue, inflammation factors(TNF alpha beta and IL-6, IL-1β), chemokines,( CXCL-1, CXCL-2,MCP-1and ICAM-1),lung permeability as well as the change of apoptosis of lung tissue cells to illustrate protective effects and mechanism of agmatine on acute lung injury in rats.Results1. In LPS-IT group and LPS-IP group, the permeability of lung tissue was increased and there was significant edema, neutrophil infiltration and structural damage.Protein concentration also increased significantly in BALF. PaO2 was lower than the normal group and the corresponding sham operation group(P <0.05). In CLP group, the normal group and the sham group were no obvious lung injury.2. By reducing tissue damage, wet / dry weight ratio and myeloperoxidase(MPO)activity of lung tissue, agmatine relieved acute lung injury induced by LPS.Accompanied in bronchoalveolar lavage fluid and lung the inflammatory cytokines(TNF-α, IL-1β and IL-6), chemokine(CXCL-1, CXCL-2, MCP-1 and ICAM-1) levels were reduced, and cell apoptosis in lung permeability and lung was also reduced.Conclusion1. In the three models of acute lung injury, there was no obvious lung injury in CLP group, but LPS-IT group and LPS-IP group were more serious. It indicated that LPS-IT group and LPS-IP group were more suitable for established model of acute lung injury and subsequent research of drugs. However, considering the stability, agility and economy of the experiment, we decided to adopt the method of intratracheal instillation of lipopolysaccharide for the subsequent experiments.2. By reducing the permeability of the lung tissue and inflammatory cytokines,chemokines in lung tissue and bronchoalveolar lavage fluid, agmatine improved the LPS-induced acute lung injury, which demonstrated that agmatine had a therapeuticeffect for ALI.