Department of Anaesthesiology, Xinjiang Medical University, Affiliated Tumour Hospital, Xinjiang, PR China.
Department of Second Pulmonary Medicine, Xinjiang Medical University, Affiliated Tumour Hospital, Xinjiang, PR China.
Can J Physiol Pharmacol. 2020 Mar;98(3):156-161. doi: 10.1139/cjpp-2019-0185. Epub 2020 Feb 20.
Hyperglycemia mediates oxidative stress, thus inducing transcription factor nuclear factor kappa B (NF-κB) activation, increasing endothelial adhesion molecule expression and monocyte/endothelial interaction, and resulting in endothelial injury. Ketamine was reported to attenuate oxidative stress in many cases. In this research, we determined whether and how ketamine protects against high-glucose-mediated augmentation of monocyte/endothelial interaction and endothelial adhesion molecule expression in human umbilical vein endothelial cells. High glucose augmented monocyte/endothelial adhesion and endothelial adhesion molecule expression. High glucose induced reactive oxygen species (ROS) production and augmented phospho-protein kinase C (p-PKC) βII expression and PKC activity. Moreover, high glucose inhibited the inhibitory subunit of nuclear factor-κBα (IκBα) expression in the cytoplasm and induced NF-κB nuclear translocation. Importantly, the effects induced by high glucose were counteracted by ketamine treatment. Further, CGP53353, a PKC βII inhibitor, inhibited high-glucose-mediated NF-κB nuclear translocation, attenuated adhesion molecule expression, and reduced monocyte/endothelial interaction. Further, these effects of ketamine against high-glucose-induced endothelial injury were inhibited by phorbol 12-myristate 13-acetate, a PKC βII activator. In conclusion, ketamine, via reducing ROS accumulation, inhibited PKC βII Ser660 phosphorylation and PKC and NF-κB activation and reduced high-glucose-induced expression of endothelial adhesion molecules and monocyte/endothelial interaction.
高血糖介导氧化应激，从而诱导转录因子核因子-κB（NF-κB）激活，增加内皮黏附分子的表达和单核细胞/内皮细胞相互作用，导致内皮损伤。氯胺酮在许多情况下被报道能减轻氧化应激。在这项研究中，我们确定了氯胺酮是否以及如何能防止高糖介导的人脐静脉内皮细胞中单核细胞/内皮细胞相互作用和内皮黏附分子表达的增强。高糖增强了单核细胞/内皮黏附作用和内皮黏附分子的表达。高糖诱导活性氧（ROS）的产生，并增加磷酸蛋白激酶 C（p-PKC）βII 的表达和 PKC 活性。此外，高糖抑制细胞质中核因子-κBα（NF-κBα）抑制亚单位的表达，并诱导 NF-κB 核易位。重要的是，氯胺酮处理能拮抗高糖引起的这些作用。此外，PKCβII 抑制剂 CGP53353 抑制高糖介导的 NF-κB 核易位，减轻黏附分子的表达，并减少单核细胞/内皮细胞的相互作用。此外，PKCβII 激活剂佛波醇 12-肉豆蔻酸 13-乙酸抑制了氯胺酮对高糖诱导的内皮损伤的这些作用。总之，氯胺酮通过减少 ROS 积累，抑制 PKCβII Ser660 磷酸化和 PKC 及 NF-κB 的激活，减少高糖诱导的内皮黏附分子和单核细胞/内皮细胞相互作用的表达。
