Spatial metabolite profiling identifies taurocholic acid as a protective mediator in hepatic ischemia-reperfusion injury: A mass spectrometry imaging and pharmacological study.

Hepatic ischemia-reperfusion injury (IRI) remains a major clinical obstacle during liver surgery and liver transplantation, and effective targeted intervention strategies are still limited. In the present study, we combined mass spectrometry imaging, in vitro cellular experiments, and in vivo animal tests to explore key functional metabolites involved in the progression of hepatic IRI. Spatial metabolite profiling via mass spectrometry imaging systematically mapped metabolic disturbances in liver tissues during IRI progression and confirmed that taurocholic acid (TCA) undergoes distinct spatial and temporal expression alterations in damaged liver regions. Subsequent pharmacological experiments verified that exogenous TCA intervention effectively alleviated hepatic IRI damage. TCA exerted prominent hepatoprotective functions, including antiapoptosis, anti-inflammation, antioxidation, and promotion of bile acid excretion. Mechanistically, TCA activated hepatic farnesoid X receptor signaling, which further suppressed excessive inflammatory responses, restrained abnormal de novo bile acid synthesis, and facilitated bile acid efflux, thereby restoring hepatic bile acid homeostasis and relieving liver injury. SIGNIFICANCE STATEMENT: This study identifies taurocholic acid (TCA) as an important protective mediator against hepatic ischemia-reperfusion injury. Our results demonstrate that mass spectrometry imaging-based spatial metabolite analysis is a powerful approach to discover functional injury-related metabolites, whereas TCA-mediated farnesoid X receptor activation provides a feasible therapeutic strategy for the prevention and treatment of hepatic ischemia-reperfusion injury.