Protein kinase C-β inhibitor treatment attenuates hepatic ischemia and reperfusion injury in diabetic rats
Protein kinase C-β inhibitor treatment attenuates hepatic ischemia and reperfusion injury in diabetic rats
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DOI：
10.3892/etm.2015.2927
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发表时间：
2016-02-01
影响因子：
2.7
通讯作者：
Wang, Yi-Jun
中科院分区：
文献类型：
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作者：
Meng, Guang-Xing;Yuan, Qiang;Wang, Yi-Jun
肝脏缺血再灌注损伤在肝切除和肝移植中起着积极的作用。虽然蛋白激酶C（PKC）-β II激活的作用和PKC-β抑制剂在糖尿病心肌I/R中的作用已被充分理解，但它们在肝脏I/R中的作用仍不清楚。本研究的目的是探讨PKC-β抑制剂对糖尿病大鼠肝脏I/R损伤的影响及其保护作用的可能机制。建立糖尿病大鼠模型，随机分为两组。这些是未接受任何治疗的未治疗组（n=10）和以5 mg/kg/天的剂量口服治疗ruboxi 2周的治疗组（n=10）。两组大鼠均行肝脏I/R。分别于I/R后1、3、5 h用酶法测定天冬氨酸转氨酶（AST）和乳酸脱氢酶（LDH）水平。采用酶联免疫吸附试验检测肿瘤坏死因子-α（TNF-α）和细胞间粘附分子1（ICAM-1）。通过免疫荧光和蛋白质印迹法分析核因子-κ B（NF-κ B）p65的表达。用Western blot法检测caspase 3的表达，用DNA Ladder法检测肝细胞凋亡。光镜和电镜观察病理变化。PKC β抑制剂治疗组血清AST和LDH水平较未治疗组降低（P
Hepatic ischemia and reperfusion (I/R) injury plays an active role in hepatic resection and transplantation. While the effects of protein kinase C (PKC)-beta II 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-kappa B (NF-kappa B) 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