Protective effect of minocycline on hepatic ischemia-reperfusion injury in rats / 中南大学学报(医学版)

ABSTRACT

Objective: To explore the protective effect of minocycline on hepatic ischemia-reperfusion injury (IRI) in rats and the underlying mechanisms. Methods: A total of 54 male Sprague-Dawley rats were randomly divided into 3 groups the sham-operated group (control group), the ischemic–reperfusion (IR group), and the minocycline preconditioning group (n=18 per group). The rats in the minocycline preconditioning group were given minocycline (45 mg/kg) by gastric irrigation at 36 h before operation and then were subsequently administered with minocycline (22.5 mg/kg) at every 12 h. hTe rats were sacriifcedat 2, 6, 24 h after reperfusion. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were measured. HE staining of liver tissues was performed to detect the histological changes, and the degree of liver IRI according to Suzuki score were calculated. hTe levels of malondialdehyde (MDA) and myeloperoxidase (MPO) were determined by spectrophotometer; the mRNA expression of tumor necrosis factor-α (TNF-α) and interleukin-1 beta (IL-1β) in the liver were measured by real-time PCR; Dickkopf-1 (DKK-1) and beta-catenin (β-catenin) protein expression in the liver were detected by Western blot. Results: Atfer 2, 6, 24 h reperfusion, compared with the IR group, the liver function (ALT, AST and LDH) in the minocycline group was signiifcantly improved (allP<0.05); the Suzuki’s scores and the levels of hepatic TNF-α and IL-1β mRNA were signiifcantly decreased (allP<0. 05); the MDA and MPO levels the liver were decreased (bothP<0.05); the protein expression of hepatic DKK-1 was decreased (P<0.05), while the protein expression of β-catenin was increased (P<0.05). Conclusion: Minocycline can alleviate the ischemic-reperfusion injury mainly through reducing oxidative stress and inhibiting the release of pro-inlfammatory cytokines depends on the activation of the Wnt/β-catenin signaling pathway in the liver.