Unfirer Sanela, Mihalj Martina, Novak Sanja, Kibel Aleksandar, Cavka Ava, Mijalevic Zrinka, Gros Mario, Brizic Ivica, Budimir Danijela, Cosic Anita, Boban Mladen, Drenjancevic Ines
Department of Physiology and Immunology, Faculty of Medicine University of Josip Juraj Strossmayer Osijek, Osijek, Croatia.
Department for Cardiovascular Diseases, Osijek University Hospital, Osijek, Croatia.
Undersea Hyperb Med. 2016 Nov-Dec;43(7):787-803.
The effects of hyperbaric oxygenation (HBO₂) on acetylcholine-induced vasorelaxation (AChIR) were evaluated in male Sprague-Dawley (SD) rats randomized into four groups: healthy controls (Ctrl), diabetic rats (DM), and control and diabetic rats that underwent hyperbaric oxygenation (Ctrl+HBO₂ and DM+HBO₂). AChIR was measured in aortic rings, with L-NAME, indomethacin, or MS-PPOH and a combination of inhibitors. mRNA expression of eNOS, iNOS, COX-1 and COX-2 was assessed by qPCR, and protein expression of CYP4A(1-3) by Western blot. Plasma antioxidative capacity and systemic oxidative stress were determined with the ferric reducing ability of plasma (FRAP) and thiobarbituric acid-reactive substances (TBARS) assays, respectively. AChIR was preserved in all groups of rats, but mediated with different mechanisms. In all experimental groups of rats, AChIR was mediated mainly by NO, with the contribution of CYP450 vasodilator metabolites. This effect was the most prominent in the DM+HBO₂ group of rats. The TBARS was significantly higher in both DM and DM+HBO₂ groups compared to respective controls. eNOS expression was upregulated in the DM+HBO₂ group compared to other groups, COX-1 expression was upregulated in the DM+HBO₂ group compared to the control. CYP450-4A1 / A2/A3protein expression was significantly higher expressed in both hyperbaric groups compared to their respective controls. In conclusion, HBO₂ affected all three vasodilator pathways and shifted AChIR to CYP450 enzymes pathway.
将雄性Sprague-Dawley（SD）大鼠随机分为四组，评估高压氧（HBO₂）对乙酰胆碱诱导的血管舒张（AChIR）的影响：健康对照组（Ctrl）、糖尿病大鼠（DM）以及接受高压氧治疗的对照和糖尿病大鼠（Ctrl+HBO₂和DM+HBO₂）。使用L-NAME、吲哚美辛或MS-PPOH以及抑制剂组合在主动脉环中测量AChIR。通过qPCR评估eNOS、iNOS、COX-1和COX-2的mRNA表达，通过蛋白质印迹法评估CYP4A(1-3)的蛋白质表达。分别用血浆铁还原能力（FRAP）和硫代巴比妥酸反应性物质（TBARS）测定法测定血浆抗氧化能力和全身氧化应激。所有大鼠组的AChIR均得以保留，但介导机制不同。在所有实验大鼠组中，AChIR主要由NO介导，CYP450血管舒张代谢产物也有贡献。这种作用在DM+HBO₂大鼠组中最为显著。与各自的对照组相比，DM组和DM+HBO₂组的TBARS均显著更高。与其他组相比，DM+HBO₂组的eNOS表达上调，与对照组相比，DM+HBO₂组的COX-1表达上调。与各自的对照组相比，两个高压氧组中CYP450-4A1 / A2/A3蛋白质表达均显著更高。总之，HBO₂影响了所有三种血管舒张途径，并使AChIR转向CYP450酶途径。
