Abstract:

Objective To investigate the effect and molecular mechanism of remimazolam on LPS⁃induced acute lung injury. Methods C57BL/6 mice were divided into normal control group，acute lung injury group，remimazolam pretreatment group and remimazolam control group，After 12 hours，the mice were sacrificed for BALF，serum and lung tissue collection. Lung injury was evaluated by HE，W/D ratio and total protein concentra⁃ tion in BALF. ELISA was used to detected the contents of TNF⁃α，IL⁃6，IL⁃1β，IL⁃10. The M1 macrophage marker iNOS + and the M2 macrophage marker CD206 + in F4/80 + macrophages were detected by flow cytometry and the mRNA and protein expressions of TNF ⁃ α，iNOS，CD206 and Arg1 were detected by real ⁃time quantitative PCR and Western blotting. Results Twelve hours after intratracheal injection of LPSA，the lung injury score，W/D ra⁃ tio and total protein concentration in BALF were significantly higher，the TNF⁃α，IL⁃6，IL⁃1β in BALF and serum was significantly increased，iNOS + macrophage was significantly increased，the mRNA and protein expressions of TNF⁃α and iNOS were significantly increased，as compared with the control group. After activated by remimazol⁃ am，the lung injury score，W/D ratio and total protein concentration in BALF were significantly decreased，the TNF⁃α，IL⁃6，IL⁃1β in BALF and serum was significantly decreased，IL⁃10 was significantly increased，iNOS + macrophage was significantly decreased，CD206 + macrophage was significantly increased，the mRNA and protein expressions of TNF⁃α and iNOS were significantly decreased，the mRNA and protein expressions of CD206 and Arg⁃ 1 were significantly increased，as compared with the LPS group. Conclusion Remimazolam alleviates LPS ⁃in⁃ duced acute lung injury by inhibiting macrophage polarization to M1 phenotype and promoting the macrophage po-larization to M2 phenotype.

Key words: sepsis, acute lung injury, macrophage polarization, remimazolam