Recombinant human insulin-like growth factor binding protein 3 attenuates lipopolysaccharide-induced acute lung injury in mice

重组人胰岛素样生长因子结合蛋白 3 减轻小鼠脂多糖诱发的急性肺损伤

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作者:Lili Kang, Xiaoying Li, Jianhong Liu, Yanfang Li, Sitao Li, Cuifen Zhao

Abstract

Acute lung injury (ALI) severely impairs gas exchange and results in high mortality. Insulin-like growth factor binding protein 3 (IGFBP-3) plays a crucial role in diverse lung diseases;however, the expression and function of IGFBP-3 in ALI remain unclear. In the present study, mice were injected with lipopolysaccharide to establish ALI, and IGF and IGFBP3 expression was measured using ELISA, western blotting, and immunohistochemical staining. Mice with ALI were then treated with recombinant human IGFBP-3 (rhIGFBP-3), and treatment was evaluated using survival analysis, histological staining analysis, and inflammatory cytokine expression in lung tissues and bronchoalveolar lavage fluid (BALF). The expression of NF-κB and VEGF was also measured using western blotting and ELISA in ALI mice. Our results demonstrated the upregulation of IGF expression in lung tissues and BALF of ALI mice, accompanied by downregulation of IGFBP-3. Administration of rhIGFBP-3 prolonged the survival time and attenuated LPS-induced lung injury. The expression of TNF-α, IL-6, IL-1β, and IFN-γ both in lung tissues and BALF decreased after rhIGFBP-3 treatment, whereas IL-10 expression increased. These results suggest that rhIGFBP-3 inhibits the expression of NF-κB and VEGF in lung tissues. Collectively, our study demonstrates a protective role of rhIGFBP-3 in ALI by regulation of lung inflammation.

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