Bindarit reduces the incidence of acute aortic dissection complicated lung injury via modulating NF-κB pathway.

Abstract

The pathogenesis of acute aortic dissection (AAD) complicated acute lung injury (ALI) is not currently well defined. At present, no effective animal model has been established for AAD complicated ALI, which hinders research and development of an appropriate treatment regimen for the concurrent conditions. The aim of the present study was to evaluate the therapeutic effects of bindarit (Bnd), an indazolic derivative, on the production of monocyte chemoattractant protein (MCP)-1 in angiotensin II (AngII)-induced complicated ALI in rats. An AAD complicated ALI rat model was established using aminopropionitrile (BAPN) and AngII. The pathological features of AAD complicated ALI were assessed via biochemical and histopathological evaluations. AngII-stimulated human pulmonary microvascular endothelial cells (hPMVECs) were used to assess the effects of Bnd on MCP-1 expression. Western blot analysis was performed to analyze the expression of proteins that may be associated with the process. AAD complicated ALI was established following BAPN and AngII interference, and a massive accumulation of macrophages was observed in the lung tissues of the study rats. Bnd was able to significantly attenuate the incidence of AAD complicated ALI (P<0.05), and significantly inhibit the accumulation of macrophages (P<0.05). The overexpression of MCP-1 induced by AngII in hPMVECs was significantly inhibited by Bnd (P<0.05), which may be associated with downregulation of the classical nuclear factor-κB pathway. Bnd was able to attenuate the incidence of AAD complicated ALI, and inhibit the accumulation of macrophages in vivo. These findings provide a basis for future applications of Bnd as part of a therapeutic treatment schedule for aortic dissection complicated lung injury.