Harmine attenuates sepsis-induced acute lung injury in rats by regulating the GPX4/ACSL4 pathway in ferroptosis

Explore the protective effect of Harmine (HM) on sepsis associated acute lung injury (SALI) rats and clarify whether it exerts its effect by regulating the glutathione peroxidase 4 (GPX4)/acyl CoA synthase 4 (ACSL4) axis to inhibit lung tissue ferroptosis. The study used cecal ligation and puncture (CLP) to induce a SALI model in rats. Sixty SPF grade male SD rats were randomly divided into five groups (n=12): sham operated (Sham) group, SALI model group, HM low-dose group (20 mg/kg), HM high-dose group (80 mg/kg), and HM high-dose+GPX4 inhibitor group (HM 80 mg/kg+RSL3 10 mg/kg). Detect changes in rat lung function using a pulmonary function detector; HE staining was used to observe pathological changes in lung tissue; The colorimetric method was used to detect the iron content, glutathione (GSH) content, and malondialdehyde (MDA) level in lung tissue; ELISA was used to detect the levels of tumor necrosis factor - α (TNF - α) and interleukin-6 (IL-6) in lung tissue; Western blot was used to detect the expression of GPX4 and ACSL4 proteins in lung tissue. The results showed that compared with the Sham group, the SALI model group rats had impaired lung ventilation function, increased lung tissue injury score, iron content, MDA levels, TNF - α and IL-6 levels, decreased GSH content and GPX4, ferritin protein expression, and increased ACSL4 protein expression. Compared with the SALI model group, the HM low and high dose groups showed an increase in the above-mentioned lung function indicators, a reduction in the degree of lung tissue damage, a decrease in injury scores, a decrease in iron content, MDA levels, TNF - α and IL-6 levels, an increase in GSH content and GPX4, ferritin protein expression, and a decrease in ACSL4 protein expression. Moreover, the high-dose group showed better results than the low-dose group; The protective effects of HM high-dose+RSL3 group were weaker than those of HM high-dose group. The above results indicate that HM can improve lung function, alleviate lung tissue damage and inflammatory response in SALI rats, and its mechanism may be by regulating the GPX4/ASCL4 axis to inhibit iron death in lung tissue, thereby improving sepsis induced acute lung injury.