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Wound healing mechanisms in rats with streptozotocin-induced diabetes mellitus

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Abstract


Background. Wound healing disorders and formation of diabetic foot, a severe disabling complication of diabetes mellitus, are accompanied by nervous system impairment and/or ischemia.

Objective — the study was aimed at assessing the effect of peripheral innervation disorders on the regulation of tissue repair in the streptozotocin-induced rat model of diabetes mellitus.

Material and methods. The study was carried out in male white outbred rats (n=70). The animals were wounded 42 days after induction of diabetes by injecting streptozotocin (diabetes group; this group received insulin Levemir at a dose of 2 units/kg in saline subcutaneously to reduce mortality), or after injection of citrate buffer (CB group). Skin samples were taken on day 8, 16, and 24 after wound modeling. Pain sensitivity was assessed in all animals. The resulting skin fragments were fixed, dehydrated, and embedded in paraffin according to standard procedures. Sections were stained with hematoxylin and eosin, antibodies specific for Ki-67, α1, β1, and β2-adrenoreceptors were used for immunohistochemical staining. Intact animals were used as an additional control group.

Results. Tail withdrawal time measured on day 56 was higher in DM group rats as compared to the control group (p=0.017). CB group demonstrated a tendency towards more rapid wounds healing than diabetic animals, although the difference was not statistically significant due to wide scatter of data in the DM group (p=0.64). The intensity of staining for Ki67 was lower in the DM group (p=0.045). Reduced density of β2-adrenoreceptors was observed at the areas remote from the wound in CB group rats.

Conclusion The results show no correlation between altered innervation and impaired tissue repair in rats with streptozotocin-induced diabetes.


Evgeniy V. Ivanov

Lomonosov Moscow State University

Email: ivanovev101@gmail.com
ORCID iD: 0000-0002-3382-4458
SPIN-code: 8191-5630

Russian Federation, 1, Leninskiye Gory, 119899 Moscow

MD

Svetlana A. Gavrilova

Lomonosov Moscow State University

Email: sgavrilova@mail.ru
ORCID iD: 0000-0002-8776-6062
SPIN-code: 9212-1137

Russian Federation, 1, Leninskiye Gory, 119899 Moscow

PhD

Maria P. Morozova

Lomonosov Moscow State University

Email: mormasha@gmail.com
ORCID iD: 0000-0002-7829-4753
SPIN-code: 2018-3418

Russian Federation, 1, Leninskiye Gory, 119899 Moscow

PhD

Ekaterina M. Klochihina

Lomonosov Moscow State University

Email: klochikhinaem@gmail.com
ORCID iD: 0000-0002-9485-3068
SPIN-code: 4202-2107

Russian Federation, 1, Leninskiye Gory, 119899 Moscow

MD

Aleksey K. Erdyakov

Lomonosov Moscow State University

Email: erdiakov@fbm.msu.ru
ORCID iD: 0000-0002-2208-5733
SPIN-code: 3983-4010

Russian Federation, 1, Leninskiye Gory, 119899 Moscow

PhD

Anna M. Gorbacheva

Endocrinology Research Centre

Author for correspondence.
Email: ann.gorbachewa@yandex.ru
ORCID iD: 0000-0001-6581-4521
SPIN-code: 4568-4179

Russian Federation, 11, Dm.Ul'yanova street, 117036 Moscow

MD

Zera N. Dzhemilova

Endocrinology Research Centre  

Email: zera1987@mail.ru
ORCID iD: 0000-0002-1129-8995
SPIN-code: 4455-5667

Russian Federation, 11, Dm.Ul'yanova street, 117036 Moscow

MD

Ekaterina V. Artemova

Endocrinology Research Centre

Email: profilaktika@bk.ru
ORCID iD: 0000-0002-2232-4765
SPIN-code: 4649-0765

Russian Federation, 11, Dm.Ul'yanova street, 117036 Moscow

MD

Gagik R. Galstyan

Endocrinology Research Centre

Email: galstyangagik964@gmail.com
ORCID iD: 0000-0001-6581-4521
SPIN-code: 9815-7509

Russian Federation, 11, Dm.Ul'yanova street, 117036 Moscow

MD, PhD, professor

Vladimir B. Koshelev

Lomonosov Moscow State University

Email: KoshelevVladimir1953@yandex.ru
ORCID iD: 0000-0003-0354-5607
SPIN-code: 2358-7046

Russian Federation, 1, Leninskiye Gory, 119899 Moscow

PhD

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Supplementary files

Supplementary Files Action
1. Fig. 1. The dynamics of wound healing in rats of different groups (M ± m). View (35KB) Indexing metadata
2. Fig. 2. Morphology of the skin of rats when stained with hematoxylin and eosin. View (3MB) Indexing metadata
3. Fig. 3. Examples of immunohistochemical staining. View (2MB) Indexing metadata
4. Fig. 4. The density of staining on the marker Ki-67 (M ± m): a - in remote areas of the skin, b - in the edge of the wound. View (50KB) Indexing metadata
5. Fig. 5. Comparison of staining density on Ki-67 in the wound edge and the distant part of the epidermis on the 8th, 16th and 24th day in the group of DM (M ± m); * - p <0.05 compared with the wound edge. View (22KB) Indexing metadata
6. Fig. 6. Intensity of β2-AR expression in different parts of the skin of rats with diabetes at different wound healing periods. View (90KB) Indexing metadata

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Copyright (c) 2018 Ivanov E.V., Gavrilova S.A., Morozova M.P., Klochihina E.M., Erdyakov A.K., Gorbacheva A.M., Dzhemilova Z.N., Artemova E.V., Galstyan G.R., Koshelev V.B.

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