Mechanisms of wound healing in rats with streptozotocin-induced diabetes mellitus

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BACKGROUND: The lack of fundamental knowledge about the role of nervous system on the physiological tissue repair  determine the applicability of pathogenetic aspects studying of wound healing formation. It was noted that the disturbance of wound healing and the formation of a diabetic foot, a severe disabling complication of diabetes mellitus, is accompanied by disorders of the nervous system and / or ischemia.

AIM: to study the effect of peripheral innervation disorders on the regulation of tissue repair in the streptozotocin model of diabetes mellitus in rats.

MATERIALS AND METHODS: The study was performed on male white mongrel rats (n = 70). Animals were wounded 42 days after modeling diabetes by injection of streptozotocin (DM group , in order to reduce mortality, this group received insulin detemir, Levemir®, at a dose of 2 units / kg in saline solution subcutaneously) or after injection of citrate buffer (CB group). Sampling of the skin was carried out on the 8th, 16th and 24th days after modeling the wound. All animals were assessed pain sensitivity. The obtained skin fragments were fixed, dehydrated and paraffin filled in a standard procedure. Sections were stained with hematoxylin and eosin, antibodies specific for Ki67, α1, β1 and β2-adrenoceptors were used for immunohistochemical staining. An intact animal was used as a control group.

RESULTS: In the DM group, the tail withdrawal time on the 56th day significantly increased in comparison with the control group (p = 0.017). In the CB group, a persistent tendency to faster wound healing is observed than in animals with diabetes, the differences are statistically insignificant p = 0.64 because of the wide spread of data in diabetic. The intensity of staining on Ki67 was significantly lower in the group of diabetes mellitus (p = 0.045). In the remote areas of the skin, a progressive decrease in the density of β2-adrenergic receptors was observed in the control group.

CONCLUSION: Morphological data indicate a worsening of regeneration processes, which was not accompanied by a statistically significant reduction in healing. There was no decrease in the density of β2-adrenergic receptors at the edges of the wound in the development of diabetes mellitus. The data obtained gives no evidence that the change in innervation precedes the disturbances in the process of tissue repair in the streptozotocin model of diabetes mellitus in rats.

About the authors

Evgeniy V. Ivanov

ФГБОУ ВО «Московский государственный университет имени М.В. Ломоносова», факультет фундаментальной медицины

ORCID iD: 0000-0002-3382-4458
SPIN-code: 8191-5630


Russian Federation, 1, Leninskiye Gory, 119899 Moscow, Russia

Svetlana A. Gavrilova


ORCID iD: 0000-0002-8776-6062
SPIN-code: 9212-1137

к.б.н., доцент

Russian Federation, 1, Leninskiye Gory, 119899 Moscow, Russia

Mariya P. Morozova


ORCID iD: 0000-0002-7829-4753
SPIN-code: 2018-3418

к.б.н., научный сотрудник

Russian Federation, 1, Leninskiye Gory, 119899 Moscow, Russia

Ekaterina M. Klochikhina


ORCID iD: 0000-0002-9485-3068
SPIN-code: 4202-2107


Russian Federation, 1, Leninskiye Gory, 119899 Moscow, Russia

Alexey K. Erdiakov


ORCID iD: 0000-0002-2208-5733
SPIN-code: 3983-4010

к.м.н., научный сотрудник

Russian Federation, 1, Leninskiye Gory, 119899 Moscow, Russia

Anna M. Gorbacheva


Author for correspondence.
ORCID iD: 0000-0001-6581-4521
SPIN-code: 9815-7509

клинический ординатор

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

Zera N. Dzhemilova


ORCID iD: 0000-0002-1129-8995
SPIN-code: 4455-5667

научный сотрудник

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

Ekaterina V. Artemova


ORCID iD: 0000-0002-2232-4765
SPIN-code: 4649-0765

научный сотрудник

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

Gagik R. Galstyan


ORCID iD: 0000-0001-6581-4521
SPIN-code: 9815-7509

доктор медицинских наук, профессор, заведующий отделением диабетической стопы

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

Vladimir B. Koshelev


ORCID iD: 0000-0003-0354-5607
SPIN-code: 2358-7046

доктор биологических наук, профессор, заведующий кафедрой

Russian Federation, 1, Leninskiye Gory, 119899 Moscow, Russia


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Abstract: 33


Copyright (c) 2021 Ivanov E.V., Gavrilova S.A., Morozova M.P., Klochikhina E.M., Erdiakov A.K., Gorbacheva A.M., Dzhemilova Z.N., Artemova E.V., Galstyan G.R., Koshelev V.B.

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