Abstract:

Objective To explore the effect of Alkaloid sinomenine（SIN）on acute lung injury in sepsis through Nrf2/Keap1 signaling pathway. Methods A rat model of sepsis was established by cecal ligation and puncture. Sixty SD rats were randomly divided into ALI group，sham operation group and SIN group（40⁃SIN group， 80⁃SIN group，160⁃SIN group），with 12 rats in each group. The severity of sepsis in each group was evaluated by scoring method；HE staining was used to observe the pathological changes of rat lung tissue，SOD and aldehyde （malondialdehyde，MDA）activity；ELISA method to detect tumor necrosis factor⁃α（TNF⁃α），interleukin（inter⁃ leukin⁃1β，IL⁃1β）and（interleukin⁃6，IL⁃6）in lung tissue ）levels. Western blot and qRT⁃PCR were used to detect the expression level of Nrf2，Keap1，HO⁃1 protein and mRNA in lung tissue，respectively. Results Compared with ALI group，40⁃SIN，80⁃SIN，and 160⁃SIN group had lower lung tissue scores in acute lung injury in sepsis （P < 0.01）. The activity of SOD was enhanced，and the level of MDA，IL⁃1β，TNF⁃α，and IL⁃6 was decreased （P < 0.01）. The interstitial edema was slight；pathological damage of the lung tissue was relieved to a certain extent. There was a dose⁃effect relationship，and the high⁃dose group had the best effect on improving the lesion degree of the lung tissue. Compared with those in ALI group，the protein and mRNA expressions of Nrf2 and HO⁃1 in the lung tissue of the 40⁃SIN，80⁃SIN and 160⁃SIN group were significantly up⁃regulated（P < 0.01），and the protein and mRNA expressions of Keap1 in the lung tissue of the rats were significantly down⁃regulated（P < 0.01）. Conclusion SIN can enhance the activity of SOD，reduce the level of MDA，IL⁃1β，TNF⁃α，IL⁃6，and regulate Nrf2/Keap1 signaling pathway，thereby alleviating the degree of lung tissue damage，protecting lung tissue，and improving acute lung disease caused by sepsis.

Key words: Alkaloid sinomenine,  , Nrf2/Keap1 signaling pathway,  , sepsis,  , acute lung injury