title: Protein kinase C-β inhibitor treatment attenuates hepatic ischemia and reperfusion injury in diabetic rats.
abstract: Hepatic ischemia and reperfusion (I/R) injury plays an active role in hepatic resection and transplantation. While the effects of protein kinase C (PKC)-βII activation and the role of PKC-β inhibitors are well understood in myocardial I/R in diabetes, they remain unclear in liver I/R. The aim of this study was to explore the effect of PKC-β inhibition and the potential mechanism by which PKC-β inhibitor treatment protects against hepatic I/R injury in diabetic rats. Diabetic rats were established and randomized into two groups. These were an untreated group (n=10), which did not receive any treatment, and a treatment group (n=10), orally treated with ruboxistaurin at a dose of 5 mg/kg/day for 2 weeks. The rats from the two groups were subjected to hepatic I/R. Aspartate transaminase (AST) and lactate dehydrogenase (LDH) levels were measured by enzymatic methods at 1, 3 and 5 h after I/R. Tumor necrosis factor-α (TNF-α) and intercellular adhesion molecule 1 (ICAM-1) were examined by enzyme-linked immunosorbent assay at the same time-points. Nuclear factor-κB (NF-κB) p65 expression was analyzed by immunofluorescence and western blotting. Apoptosis of hepatic cells was examined by the western blot analysis of caspase 3 expression and by DNA ladder analysis. Pathological changes were examined using light and electron microscopy. Serum AST and LDH levels in the PKC-β inhibitor treatment group were diminished compared with those in the untreated group (P<0.01). Serum TNF-α and ICAM-1 (P<0.01) levels were also decreased at different time-points in the PKC-β inhibitor treatment group. The relative expression of NF-κB p65 and caspase 3 in the hepatic tissue was weakened in the PKC-β inhibitor treatment group compared with that in the untreated group (P<0.01). Pathological changes in hepatic tissue were attenuated by the PKC-β inhibitor. In conclusion, PKC-β inhibitor treatment protected against liver I/R injury in diabetic rats. The mechanisms probably involved the attenuation of microvascular injury, reduced transport of injury-associated factors and diminishment of the activation of NF-κB p65.
authors.affiliation: Department of Hepatobiliary Surgery, Tianjin Hepatobiliary Research Institute, Tianjin Third Central Hospital, Tianjin 300170, P.R. China.
authors.forename: Guang-Xing
authors.initials: GX
authors.lastname: Meng
authors.affiliation: Department of Hepatobiliary Surgery, Tianjin Hepatobiliary Research Institute, Tianjin Third Central Hospital, Tianjin 300170, P.R. China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: Department of Cardiology, Tianjin Union Medicine Center, Tianjin 300121, P.R. China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Wei
authors.affiliation: Department of Gastrointestinal Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Meng
authors.affiliation: Department of Hepatobiliary Surgery, Tianjin Hepatobiliary Research Institute, Tianjin Third Central Hospital, Tianjin 300170, P.R. China.
authors.forename: Yi-Jun
authors.initials: YJ
authors.lastname: Wang
keywords: diabetes; hepatic ischemia/reperfusion injury; protein kinase C-β inhibitor