[Action mechanism of Total Crocin Tablets in treatment of rhabdomyolysis-induced acute kidney injury based on proteomics].

Rhabdomyolysis-induced acute kidney injury( AKI) lacks specific treatment drugs. This study investigated the protective effect and mechanism of Total Crocin Tablets against this disease. Rat models of AKI were induced by injecting 50% glycerol into the hind limbs. They were randomly divided into a normal control group, a model group, Total Crocin Tablet low-(7. 5 mg·kg~(-1)·d~(-1)), medium-(15 mg·kg~(-1)·d~(-1)), high-dose(30 mg·kg~(-1)·d~(-1)) groups, and a catechin group(80 mg·kg~(-1)·d~(-1)). Prophylactic administration was given by gavage for seven days, and evaluation was conducted 24 h after modeling. The results show that Total Crocin Tablets significantly reduce the levels of serum creatinine(SCr), blood urea nitrogen(BUN), and creatine kinase(CK) in serum in a dose-dependent manner, improving renal function and muscle injury. The levels of interleukin(IL)-1β, IL-6, and tumor necrosis factor-α( TNF-α) in serum are decreased. The myoglobin( Mb) expression in both serum and kidney tissue is downregulated. The superoxide dismutase( SOD) activity is increased, while the levels of lactate dehydrogenase( LDH) and malondialdehyde( MDA) are decreased, thereby alleviating oxidative stress. The pathological damage in muscle and kidney is attenuated. Tandem mass tag(TMT)-based quantitative proteomics was used to screen 13 differentially expressed proteins, both fatty acid-binding protein 4(FABP4) and alpha-1-acid glycoprotein 1(ORM1) were significantly upregulated in the kidneys of the model group, while treatment with Total Crocin Tablets reversed this change. These differentially expressed proteins were primarily enriched in pathways related to fatty acid degradation, peroxisome proliferator-activated receptor(PPAR) signaling, glutathione metabolism, and inflammatory response. Western blot validation confirmed the downregulation of FABP4 and ORM1 expression. In conclusion, Total Crocin Tablets protect against rhabdomyolysis-induced AKI by downregulating multiple targets such as FABP4 and ORM1, regulating lipid metabolism, and inhibiting inflammation and oxidative stress, thereby providing a basis for clinical translation.