PMID- 26893648 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220317 IS - 1792-0981 (Print) IS - 1792-1015 (Electronic) IS - 1792-0981 (Linking) VI - 11 IP - 2 DP - 2016 Feb TI - Protein kinase C-beta inhibitor treatment attenuates hepatic ischemia and reperfusion injury in diabetic rats. PG - 565-570 AB - Hepatic ischemia and reperfusion (I/R) injury plays an active role in hepatic resection and transplantation. While the effects of protein kinase C (PKC)-betaII activation and the role of PKC-beta 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-beta inhibition and the potential mechanism by which PKC-beta 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-alpha (TNF-alpha) and intercellular adhesion molecule 1 (ICAM-1) were examined by enzyme-linked immunosorbent assay at the same time-points. Nuclear factor-kappaB (NF-kappaB) 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-beta inhibitor treatment group were diminished compared with those in the untreated group (P<0.01). Serum TNF-alpha and ICAM-1 (P<0.01) levels were also decreased at different time-points in the PKC-beta inhibitor treatment group. The relative expression of NF-kappaB p65 and caspase 3 in the hepatic tissue was weakened in the PKC-beta inhibitor treatment group compared with that in the untreated group (P<0.01). Pathological changes in hepatic tissue were attenuated by the PKC-beta inhibitor. In conclusion, PKC-beta 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-kappaB p65. FAU - Meng, Guang-Xing AU - Meng GX AD - Department of Hepatobiliary Surgery, Tianjin Hepatobiliary Research Institute, Tianjin Third Central Hospital, Tianjin 300170, P.R. China. FAU - Yuan, Qiang AU - Yuan Q AD - Department of Hepatobiliary Surgery, Tianjin Hepatobiliary Research Institute, Tianjin Third Central Hospital, Tianjin 300170, P.R. China. FAU - Wei, Li-Ping AU - Wei LP AD - Department of Cardiology, Tianjin Union Medicine Center, Tianjin 300121, P.R. China. FAU - Meng, Hua AU - Meng H AD - Department of Gastrointestinal Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China. FAU - Wang, Yi-Jun AU - Wang YJ AD - Department of Hepatobiliary Surgery, Tianjin Hepatobiliary Research Institute, Tianjin Third Central Hospital, Tianjin 300170, P.R. China. LA - eng PT - Journal Article DEP - 20151209 PL - Greece TA - Exp Ther Med JT - Experimental and therapeutic medicine JID - 101531947 PMC - PMC4734052 OTO - NOTNLM OT - diabetes OT - hepatic ischemia/reperfusion injury OT - protein kinase C-beta inhibitor EDAT- 2016/02/20 06:00 MHDA- 2016/02/20 06:01 PMCR- 2015/12/09 CRDT- 2016/02/20 06:00 PHST- 2014/04/24 00:00 [received] PHST- 2014/12/12 00:00 [accepted] PHST- 2016/02/20 06:00 [entrez] PHST- 2016/02/20 06:00 [pubmed] PHST- 2016/02/20 06:01 [medline] PHST- 2015/12/09 00:00 [pmc-release] AID - ETM-0-0-2927 [pii] AID - 10.3892/etm.2015.2927 [doi] PST - ppublish SO - Exp Ther Med. 2016 Feb;11(2):565-570. doi: 10.3892/etm.2015.2927. Epub 2015 Dec 9.