Abstract: Objective To investigate the mechanism by which evodiamine alleviates blood transfusion related acute lung injury (TRALI) in rats by regulating high mobility group protein Bl (HMGB1)/ toll like receptor 4 (TLR4)/nuclear transcription factor-κB (NF-κB) signaling pathway. Methods A total of 72 SD rats were randomly divided into the model group, low-dose evodiamine group, high-dose evodiamine group, no load group, high-dose evodiamine+HMGB1 overexpression group, and control group with 12 rats in each. Except for the control group, the TRALI model was prepared by intraperitoneal injection of lipopolysaccharide (LPS) combined with infusion of human plasma. After that, we analyzed the lung function indexes such as inspiratory resistance (Ri), minute ventilation (MV) and peak expiratory flow (PEF). Then, in each group we examined the lung wet-dry ratio of rats and the pathological changes of lung tissue by hematoxylin-eosin (HE) staining; the platelet and neutrophil aggregation in lung tissue by immunofluorescence staining; the total number of cells and the percentage of neutrophils in bronchoalveolar lavage fluid (BALF); the levels of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in BALF and serum by enzyme-linked immunosorbent assay (ELISA); as well as the expression of HMGB1/TLR4/NF-κB signaling pathway-related proteins in lung tissue by western blotting. Results Compared with the model group, the pulmonary function indexes MV and PEF in low-dose evodiamine group and high-dose evodiamine group were increased (P<0.05), while Ri, lung wet-dry ratio, lung histopathological score, platelet-neutrophil optical density in lung tissue, total number of cells in BALF, percentage of neutrophils, levels of pro-inflammatory factors TNF-α and IL-1β in BALF and serum, HMGB1 and TLR4 protein expression in lung tissue and p-NF-κB p65/NF-κB p65 were all decreased (P<0.05). Overexpression of HMGB1 attenuated the improvement of lung function by evodiamine in TRALI rats. Conclusion Evodiamine may inhibit the inflammation in TRALI rats by inhibiting the activation of HMGB1/TLR4/NF-κB signaling, thereby reducing its acute lung injury, and repairing its lung function.

Key words: Evodiamine, High mobility group protein Bl/toll like receptor 4/nuclear transcription factor-κB signaling pathway, Blood transfusion related acute lung injury, Inflammation, Lung function