Experimental study of the pattern of genes activated by multi-day intermittent hypoxia in the rat pancreas

Abstract

Intermittent hypoxia affects a variety of pathological conditions in the body and is used in medicine to reproduce the sanogenic therapeutic effect. Intermittent hypoxia is used for clinical indications to improve lung function; increase the body’s adaptive capacity; in obstructive sleep apnoea syndrome; in anaemia, diabetes mellitus. In cancer radiotherapy, intermittent hypoxic training helps to increase the sensitivity of the tumour to treatment. Intermittent hypoxia is useful in rehabilitation medicine to improve the physical recovery of patients after surgery or injury to improve the body’s functional capabilities. However, to date, the activity of regulatory genes, that activate the molecular mechanisms of the above-mentioned sanogenic effects of intermittent hypoxia has not been sufficiently studied. The aim of the study: to determine the expression of hypoxia-related genes in pancreas of Wistar rats under intermittent hypoxia. Materials and methods. The CFX-96 Touch™ real-time reverse transcription polymerase chain reaction (PCR) (Bio-Rad, USA) and the RT2 Profiler™ PCR Array Rat Hypoxia Signalling Pathway kit (QIAGEN, Germany) were used to analyse gene expression in experimental animals, where 84 genes involved in the hypoxia signalling pathway identified in the pancreas were studied. Results. According to the results of PCR analysis of pancreatic samples from intact animals and animals exposed to hypoxic training, the activity of the gene panel can be distributed as follows: genes with high expression compared to the intact group of animals, genes with low expression compared to the intact group of animals and genes in which no significant changes were detected in the samples compared to the intact group of animals. We have found, that the genes Cops5, F10, Jmjd6, Lgals3, Rbpjl, Vegfa have high expression activity compared to the intact group of animals. Conclusions. The increase in the expression of Cops5 by 10.29 times, Lgals3 by 2.94 times and Rbpjl by 5.73 times as a result of intermittent hypoxia can be regarded as an activating factor for the increase in the proliferation of endocrine and exocrine pancreatic cells and the growth of their antiapoptotic potential. The 3.20-fold increase in Jmjd6 gene expression under intermittent hypoxia can be interpreted as a regulatory effect through protein dehydroxylation and promotion of antiapoptotic protein activity in endocrine and exocrine pancreatic cells. The 5.99-fold increased level of Vegfa expression may promote angiogenesis in the pancreas under intermittent hypoxia.