Protein kinase C-β inhibitor treatment attenuates hepatic ischemia and reperfusion injury in diabetic rats

Meng,Guang‑Xing; Yuan,Qiang; Wei,Li‑Ping; Meng,Hua; Wang,Yi‑Jun

doi:10.3892/etm.2015.2927

Protein kinase C-β inhibitor treatment attenuates hepatic ischemia and reperfusion injury in diabetic rats

Authors:
- Guang‑Xing Meng
- Qiang Yuan
- Li‑Ping Wei
- Hua Meng
- Yi‑Jun Wang
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Affiliations: Department of Hepatobiliary Surgery, Tianjin Hepatobiliary Research Institute, Tianjin Third Central Hospital, Tianjin 300170, P.R. China, Department of Cardiology, Tianjin Union Medicine Center, Tianjin 300121, P.R. China, Department of Gastrointestinal Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China
Published online on: December 9, 2015 https://doi.org/10.3892/etm.2015.2927
Pages: 565-570

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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.

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