Effect of integrin CD11b on liver ischemia/reperfusion injury in mice and underlying mechanism / 中华器官移植杂志

ABSTRACT

Objective To investigate the role of integrin CD11b in liver ischemia/reperfusion (I/R) injury and its possible mechanism.Method CD11b-/-and WT (C57BL/6) mice were used to establish a 70％ liver warm I/R by clamping the left and median liver lobes for 60 min with vascular micro clamp at 37℃,then the clamp was removed and the abdominal incision was sutured.The blood plasma and liver samples were obtained at different time points (1,3,6,12,24 and 48 h) postreperfusion to assess liver function and cellular injury.Serum ALT and AST levels were determined,and HE staining and TUNEL assay were performed to estimate the severity of liver damage.Tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) were assayed by Reverse transcription polymerase chain reaction (RT-PCR).Kupffer cells were isolated from the live,and the reduced form of nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase activity and active oxygen species (ROS) production were assayed.Result CD11b-/-mice displayed a significantly preserved liver function as represented by lower alanine aminotransferase (ALT) and aspartic transaminase (AST) levels,less histological damage and apoptosis compared to WT mice.Furthermore,TNF-α was decreased and IL-10 mRNA expression was increased in CD11b-/-mice compared to WT mice.Finally,CD11b-/-mice showed decreased activity of NADPH oxidase and less ROS production.Conclusion Integrin CD11 b may regulate the levels of inflammatory (TNF-α) and anti-inflammatory (IL-10) cytokines,enhance the activity of NADPH oxidase in Kupffer cells and enrich the production of ROS,which aggravate liver I/R injury.