Mechanism of MCP-1 in Acute Lung Injury and Advanced Therapy by Drug-Loaded Dextrin Nanoparticle. (27th September 2018)

• Record Type: Journal Article
• Authors: Cao, Zheng; Liu, Jing-Lan; Wu, Shen; Wang, Qiao
• Other Names: Ding Jianxun Academic Editor.
• Is Part Of: International journal of polymer science. Volume 2018(2018)
• Publication Date: 2018-09-27
• Subjects: Polymers -- Periodicals; Polymers; Periodicals; 547.7
• DOI: 10.1155/2018/9269154
• Languages: English
• ISSNs: 1687-9422

Abstract

Abstract : Objective . To observe the expression of monocyte chemotactic protein 1 (MCP-1) in acute lung injury (ALI) rat model, to characterize its effect on the development and progression of ALI, and to identify the potential new drug delivery approach during in vivo experiment. Method . The effects of different doses of lipopolysaccharide (LPS) on human pulmonary artery endothelial cells (HPAEC) were tested. For the animal experiments, thirty Sprague-Dawley (SD) rats were divided into physiological saline control group (NC group), the LPS model group (L group), the antagonist RS102895 combined with LPS group (R + L group), and the antagonist RS102895-loaded polyaldehyde dextran nanoparticles combined with LPS group (DNPR + L group). The blood gas analysis and dry/wet weight ratio were detected 24 hours after interventions. The levels of inflammatory factors, tumor necrosis factor- α (TNF- α ) and interleukin-1 β (IL-1 β ), were tested by ELISA. The expression of monocyte chemoattractant protein-1 (MCP-1) in lung tissues was examined through Western blot, and the change of MCP-1 mRNA expression level was detected by performing RT-PCR. Result . LPS was responsible for inducing ALI in rats, and the degree of cell damage was dose-dependent. Blood gas analysis of L group showed that PaO2 and PaO2/FiO2 levels were significantly lower than those of the NC group (P < 0.05 ), while the dry/wet weight ratio of lung tissues in L group increased (P < 0.05 ). Inflammatory factors including TNF- α and IL-1 β and the expression of MCP-1 in both protein and mRNA levels were higher in L group than in the NC group (P < 0.05 ). The inhibition of the interaction between MCP-1 and chemokines receptor 2 (CCR2) by antagonist RS102895 can significantly alleviate the ALI in rats, which is accompanied by a significant decrease of inflammatory factors and MCP-1 expression (P < 0.05 ). Compared with R + L group, treatment with DNPR and LPS combination significantly improved the condition of rats and decreased the level of TNF- α, IL-1 β, and MCP-1 expression (P < 0.05 ). Conclusion . In ALI, RS102895 can inhibit the MCP-1/CCR2 interaction, therefore, retarding the progress of ALI. Because of the high transfection efficiency of inhibitor RS102895packgaed by polyaldehyde dextran nanoparticles, this phenomenon particularly reached a significant level. The results imply new insights for the treatment of ALI.