Solymar Margit, Ivic Ivan, Balasko Marta, Fulop Balazs D, Toth Gabor, Tamas Andrea, Reman Gyongyver, Koller Akos, Reglodi Dora
1 Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary.
2 Department of Anatomy, MTA-PTE PACAP Research Team, Centre for Neuroscience, Medical School, University of Pécs, Pécs, Hungary.
Diab Vasc Dis Res. 2018 Jul;15(4):277-285. doi: 10.1177/1479164118757922. Epub 2018 Feb 21.
Short-lasting hyperglycaemia occurs frequently in prediabetes and poorly controlled diabetes mellitus leading to vascular damage. Pituitary adenylate cyclase-activating polypeptide (PACAP) has been shown to play a protective role in vascular complications of diabetes; moreover, antioxidant effects of PACAP were also described. Therefore, we hypothesized that PACAP exerts protective effects in short-term hyperglycaemia-induced vascular dysfunctions.
After short-term hyperglycaemia, acetylcholine-induced and sodium nitroprusside-induced vascular relaxation of mouse carotid arteries were tested with a myograph with or without the presence of PACAP or superoxide dismutase. Potential direct antioxidant superoxide-scavenging action of pituitary adenylate cyclase-activating peptide was tested with pyrogallol autoxidation assay; furthermore, the effect of pituitary adenylate cyclase-activating peptide or superoxide dismutase was investigated on hyperglycaemia-associated vascular markers.
PACAP administration resulted in reduced endothelial dysfunction after a 1-h hyperglycaemic episode. PACAP was able to restore acetylcholine-induced relaxation of the vessels and improved sodium nitroprusside-induced relaxation. This effect was comparable to the protective effect of superoxide dismutase, but PACAP was unable to directly scavenge superoxide produced by autoxidation of pyrogallol. Endothelial dysfunction was associated with elevated levels of fibroblast growth factor basic, matrix metalloproteinase 9 and nephroblastoma overexpressed gene proteins. Their release was reduced by PACAP administration.
These results suggest a strong protective role of PACAP in the vascular complications of diabetes.
短暂性高血糖在糖尿病前期和控制不佳的糖尿病中频繁发生，会导致血管损伤。垂体腺苷酸环化酶激活多肽（PACAP）已被证明在糖尿病血管并发症中发挥保护作用；此外，还描述了PACAP的抗氧化作用。因此，我们推测PACAP在短期高血糖诱导的血管功能障碍中发挥保护作用。
短期高血糖后，使用肌张力测定仪检测有无PACAP或超氧化物歧化酶存在时，小鼠颈动脉对乙酰胆碱诱导和硝普钠诱导的血管舒张情况。用邻苯三酚自氧化法检测垂体腺苷酸环化酶激活肽潜在的直接抗氧化超氧化物清除作用；此外，研究了垂体腺苷酸环化酶激活肽或超氧化物歧化酶对高血糖相关血管标志物的影响。
给予PACAP可减轻1小时高血糖发作后的内皮功能障碍。PACAP能够恢复乙酰胆碱诱导的血管舒张，并改善硝普钠诱导的血管舒张。这种作用与超氧化物歧化酶的保护作用相当，但PACAP无法直接清除邻苯三酚自氧化产生的超氧化物。内皮功能障碍与碱性成纤维细胞生长因子、基质金属蛋白酶9和肾母细胞瘤过度表达基因蛋白水平升高有关。给予PACAP可减少它们的释放。
这些结果表明PACAP在糖尿病血管并发症中具有强大的保护作用。
