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

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

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
 
 

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

аспирант

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

Svetlana A. Gavrilova

 
 

Email: sgavrilova@mail.ru
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

 
 
 

Email: mormasha@gmail.com
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

 
 
 

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

аспирант

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

Alexey K. Erdiakov

 
 
 

Email: erdiakov@fbm.msu.ru
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.
Email: ann.gorbachewa@yandex.ru
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

 
 

Email: zera1987@mail.ru
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

 
 

Email: profilaktika@bk.ru
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

 
 

Email: galstyangagik964@gmail.com
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

 
 
 

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

доктор биологических наук, профессор, заведующий кафедрой

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

References

  1. Токмакова А.Ю., Страхова Г.Ю., Арбузова М.И. Особенности хронических ран у больных сахарным диабетом и пути их коррекции // Эндокринная хирургия. - 2007. - № 1. - C. 38–42. [Tokmakova A. Yu., Strakhova G. Yu., Arbuzova M. I. Osobennosty chronicheskih ran u bolnykh sakharnym diabetom i puti ih korrektsiy. Endocrinnaya Khirurgia. 2007; 1: 38-42 (In Russ)].
  2. Garwood C.S., Steinberg J.S., Kim P.J. Bioengineered Alternative Tissues in Diabetic Wound Healing // Clin Podiatr Med Surg 2015. № 1 (32). P. 121–133. doi: 10.1016/j.cpm.2014.09.004.
  3. Demidova-Rice T.N., Hamblin M.R., Herman I.M. Acute and impaired wound healing: pathophysiology and current methods for drug delivery, part 1: normal and chronic wounds: biology, causes, and approaches to care. // Adv Skin Wound Care. 2012. № 7. V. 25. P. 304–314. doi: 10.1097/01.ASW.0000416006.55218.d0.
  4. Roosterman D. Goerge T., Schneider S.W. et al. Neuronal control of skin function: the skin as a neuroimmunoendocrine organ. // Physiol Rev. 2006. № 4 (86). P. 1309–1379. doi: 10.1152/physrev.00026.2005
  5. Grando S.A., Pittelkow M.R., Schallreuter K.U. Adrenergic and cholinergic control in the biology of epidermis: physiological and clinical significance. // J Invest Dermatol. 2006. № 9 (126). P. 1948–1965. doi: 10.1038/sj.jid.5700151
  6. Grando S.A. Kist D. A., Qi M. et al. Human keratinocytes synthesize, secrete, and degrade acetylcholine. // J Invest Dermatol. 1993. № 1 (101). P. 32–36.
  7. Inoue R., Yoshihisa Y., Tojo Y. et al.. Localization of serine racemase and its role in the skin. // J Invest Dermatol. 2014. № 6 (134). P. 1618–26. doi: 10.1038/jid.2014.22.
  8. Pullar C. Manabat-Hidalgo C. G., Bolaji R.S. et al. β-Adrenergic receptor modulation of wound repair // Pharmacol Res. 2008. № 2 (58). P. 158–164. doi: 10.1016/j.phrs.2008.07.012.
  9. Ramaekers J., Lamers J., Verhey F. et al. A comparative study of the effects of carbamazepine and the NMDA receptor antagonist remacemide on road tracking and car-following performance in actual traffic // Psychopharmacology (Berl). 2002. № 2 (159). P. 203–210. doi: 10.1007/s002130100898.
  10. Biessels G.J., Bril V., Calcutt N. A. et al. Phenotyping animal models of diabetic neuropathy: a consensus statement of the diabetic neuropathy study group of the EASD (Neurodiab). // J Peripher Nerv Syst. 2014. № 2 (19). P. 77–87. doi: 10.1111/jns5.12072.
  11. Румянцев П.О., Саенко В.А., Румянцева У.В. и др. Статистические методы анализа в клинической практике. Часть 2. Анализ выживаемости и многомерная статистика // Проблемы эндокринологии. - 2009. -№55. - C. 48–56. [Rumyantsev P. O., Saenko V. A., Rumyantseva U. V. et al. Statistical methods for the analyses in clinical practice. Part 2. Survival analysis and multivariate statistics. Problemy Endocrinologii. 2009; 55: 48-56. (In Russ)].
  12. Yorek M.A. Alternatives to the Streptozotocin-Diabetic Rodent // Int Rev Neurobiol. 2016; 127: P. 89–112 doi: 10.1016/bs.irn.2016.03.002.

Supplementary files

There are no supplementary files to display.

Statistics

Views

Abstract: 33

PlumX


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.

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies