17β-estradiol ameliorates LPS-induced acute lung injury via mediating mitochondrial biogenesis and function in rats.

Sepsis-induced acute lung injury (ALI), and its severe manifestation, acute respiratory distress syndrome (ARDS), are complex conditions associated with high global mortality. 17β-estradiol (E2), a sex hormone, is implicated in ARDS pathophysiology, but its mechanisms remain unclear. In this study, we explored the role of E2 in sepsis-induced ALI using ovariectomized female Sprague-Dawley rats and A549 cells. Endogenous E2 levels were assessed via the uterus-to-body weight ratio and serum E2 concentrations. Our findings demonstrate that E2 deficiency exacerbates LPS-induced mitochondrial damage, apoptosis, and lung injury, while exogenous E2 reverses these effects. Mechanistically, E2 promotes mitochondrial biogenesis through activation of the PGC-1β/Nrf2/TFAM signaling pathway. These results suggest that exogenous E2 may offer a promising therapeutic approach for ARDS by enhancing mitochondrial function and reducing apoptosis.