PROTEOLYTIC IMBALANCE AS A KEY FACTOR OF THE DEVELOPMENT OF CHRONIC PANCREATITIS WITH AND WITHOUT TYPE 1 DIABETES MELLITUS

Raksha N. G., Halenova T. I., Vovk T. B., Sukhodolia S. A., Beregova T. V., Ostapchenko L. I.

CLINICAL AND EXPERIMENTAL MEDICINE

Scentific article

According to world statistics, the overall incidence of chronic pancreatitis is about 50 per 100.000 people, but its prevalence tend to grow rapidly. Despite a numerous researches, the underlying mechanisms, which cause the progression of chronic pancreatitis and increase risk of pancreatitis-associated complications have not been clearly elucidated. Pancreatitis is accompanied by the progressive tissue damage leading to the functional insufficiency of the pancreas. Among these disturbances is the pancreatic fibrosis, which firstly resulted from the disorders of extracellular matrix proteins metabolism. The main enzymes involved in extracellular matrix remodeling are matrix metalloproteinases. The present finding has shown the increase of the level of MMPs, such as MMP-2 and MMP-9 in the liver and pancreas of the rats with CP as well as CP+DT1. Besides the local action within the organs, MMPs could release from the damaged tissue into the bloodstream and affect distant organs. The increased level of both MMPs in the serum of the rats with CP and CP+DT1 confirms the systemic effect of the pancreatitis. It is well known that the chronic pancreatitis is strongly related to inflammation. Inflammatory reactions first occur in a pancreas as local, but may amplify and lead to development of systemic inflammation. Long-term inflammatory process mediates irreversible destruction of pancreatic parenchyma and ductal structures with further fibrous scar tissue formation. These alterations are considered as key triggers of some pancreatitis-associated complications, namely fibrosis or/and malignant transformation. The significant increase of the level of cytokines in the serum, pancreas, and liver at the 134th day of experiment could serve as evidence of the immune imbalance and has indicated the development both systemic and local inflammation. The protein level under the pancreatitis condition has also been investigated. In our experiment, the reduction of protein content was observed in the liver and pancreas of the rats with CP and CP+DT1. Since diabetes type 1 has been recognized as inflammatory state, this may be the reason that mediated more significant change of total protein concentration in the group of the rats suffering from diabetes type 1. The opposite change of protein level was detected in the serum of the rats – in this case the protein concentration was increased in the rats both experimental groups. The concentration of peptides in the serum and their content in the liver and pancreas of the rats were also increased. It could be due to the intensification of catabolic processes as well as the impairment elimination of these molecules from the bloodstream. A set of peptides in the biological fluids and tissues represents the peptide pools, which are important for maintenance of homeostasis. The components of the peptide pools exert a modulation effect on nervous, endocrine, immune, cardiovascular and other systems. This effect is complex and implemented by all peptides presented in the pool. The results of chromatographic analysis of the peptide pools derived from the tissue of the rats with chronic pancreatitis revealed the alterations of peptide repertoire. The main change includes the appearance of peptides that were absent in the control group.

chronic pancreatitis, diabetes type 1, proteolysis, peptide pool

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«Bulletin of problems biology and medicine» Issue 3 (152), 2019 year, 186-191 pages, index UDK 577.112.7:612.115

10.29254/2077-4214-2019-3-152-186-191