The effects of gene therapy with PEI-pDNA complex containing human preproinsulin gene on structural and ultrastructural characteristics of several organs in mice of different ages at experimental diabetes mellitus

Home/2018, Vol. 6, No. 1/The effects of gene therapy with PEI-pDNA complex containing human preproinsulin gene on structural and ultrastructural characteristics of several organs in mice of different ages at experimental diabetes mellitus

Cell and Organ Transplantology. 2018; 6(1):48-56.
DOI: 10.22494/COT.V6I1.81

The effects of gene therapy with PEI-pDNA complex containing human preproinsulin gene on structural and ultrastructural characteristics of several organs in mice of different ages at experimental diabetes mellitus

Kvitnitskaya-Ryzhova T. Yu.1, Lugovskoy S. P.1, Klymenko P. P.1, Mykhalsky S. A.1, Khablak G. V.1, Toporova O. K.2
1D. F. Chebotarev State Institute of Gerontology of the National Academy of Medical Sciences of Ukraine, Kyiv, Ukraine
2Institute of Molecular Biology and Genetics of the National Academy of Sciences of Ukraine, Kyiv, Ukraine

Abstract
Diabetes mellitus (DM) is one of the leading age-related diseases. Its prevalence, according to WHO, will increase steadily, therefore the study of the age-related features of its morphogenesis and search for new approaches to its treatment, taking into account the age, remains one of the topical issue of modern medicine and biology. The purpose of the research was to study the age-related features of the effect of gene therapy with PEI-pDNA complex containing the human preproinsulin gene on the morpho-functional characteristics of organs mostly affected by diabetic dysfunction at streptozotocin-induced DM in mice of different ages.
Materials and methods. DM was induced in 3- and 20-month old mice by the administration of streptozotocin (40 mg/kg on 0.1 M citrate buffer, once a day, for 5 days). Four weeks after the development of persistent hyperglycemia, the polyethylenimine (PEI)-plasmid DNA complex, containing the human preproinsulin gene, was injected into the liver. On the 30th day after the plasmid administration, morphofunctional features of the pancreas, myocardium, liver and kidney of young and old mice were studied using histological, electron microscopic, histochemical and immunohistochemical techniques.
Results. In the young animals, the use of the PEI-pDNA complex with the human preproinsulin gene had a certain healing effect on the structure and ultrastructure of the studied organs, reduced the dystrophic and destructive alterations in the cells of their parenchyma and capillaries, reduced the intensity of apoptosis, and stimulated the development of compensatory-adaptive hyperplastic processes. In the old animals, there was a slight positive effect of the gene therapy or no effects. Often, some of the structural and ultrastructural parameters of several organs worsened; the high intensity of apoptosis and the development of complications (insulitis) persisted.
Conclusions. The effect of the PEI-pDNA complex containing the human preproinsulin gene on the morpho-functional characteristics of internal organs in mice at DM has different efficacy at different ages: high in the young animals and minor effect, lack of it, or additional deterioration in the old ones, which manifested itself in various tissues in different degree.

Key words:  diabetes mellitus; gene therapy; preproinsulin; apoptosis; aging

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Kvitnitskaya-Ryzhova T, Lugovskoy S, Klymenko P, Mykhalsky S, Khablak G, Toporova O. The effects of gene therapy with PEI-pDNA complex containing human preproinsulin gene on structural and ultrastructural characteristics of several organs in mice of different ages at experimental diabetes mellitus. Cell and Organ Transplantology. 2018; 6(1):48-56. doi:10.22494/cot.v6i1.81

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