problendoПроблемы ЭндокринологииProblems of Endocrinology0375-96602308-1430Endocrinology Research Centre10.14341/probl201258613-18problendo-58Research ArticleСтатьиArticlesПредикторы развития хронических раневых дефектов мягких тканей нижних конечностей у пациентов с сахарным диабетом 1-го типа и липоидным некробиозомPredictors of the development of chronic wound defects in the soft tissues of the lower extremities in the patients with type 1 diabetes mellitus and lipoid necrobiosisSemenovaD. A.dsmirnoff@list.ruRepinaE. A.dsmirnoff@list.ruStepanovaS. M.dsmirnoff@list.ruProkofievS. A.dsmirnoff@list.ruMatushevskayaE. V.dsmirnoff@list.ruTokmakovaA. Yu.dsmirnoff@list.ruФГБУ ≪Эндокринологический научный центр≫ МЗ РФРоссияEndocrinology Research Centre, Moscow, Russian FederationRussian FederationФГОУ Институт повышения квалификации Федерального медико-биологического агентства РФ, МоскваРоссияInstitute for Advanced Studies of the Federal Medical and Biological Agency, Moscow, Russian FederationRussian Federation2012140520135861318Copyright © Semenova D.A., Repina E.A., Stepanova S.M., Prokofiev S.A., Matushevskaya E.V., Tokmakova A.Y., 20122012Semenova D.A., Repina E.A., Stepanova S.M., Prokofiev S.A., Matushevskaya E.V., Tokmakova A.Y.Semenova D.A., Repina E.A., Stepanova S.M., Prokofiev S.A., Matushevskaya E.V., Tokmakova A.Y.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.probl-endojournals.ru/jour/article/view/58

Клинико-иммунологическое обследование проведено 50 пациентам с сахарным диабетом 1-го типа (СД1). Пациенты были разделены на две группы: 25 пациентов с СД1 и липоидным некробиозом (ЛН) и 25 пациентов с СД1 без ЛН. Экспрессию Толл-подобных рецепторов — TLR2 , TLR3, TLR4 определяли на моноцитах и нейтрофилах периферической крови. Оценивали периферический кровоток и иннервацию нижних конечностей. Установлено, что снижение экспрессии и интенсивности флюоресценции TLR2 и TLR4 на моноцитах и TLR3 на нейтрофилах ассоциировано с выраженностью поражения кожи у пациентов с ЛН и СД1. Таким образом, определение TLR у пациентов с СД1 и ЛН может быть использовано для прогнозирования течения дерматоза.

A total of 50 patients presenting with type 1 diabetes mellitus (DM1) were available for the clinical and immunological examination. They were allocated to two groups, one comprised of 25 patients with DM1 and lipoid necrobiosis (LN), the other consisting of 25 patients with DM1 without LN. Expression of Toll-like receptors (TLR2, TLR3, and TLR4) was evaluated in monocytes and neutrophils obtained from peripheral blood. In addition, the state of peripheral circulation and innervation of the lower extremities was evaluated. It was shown that the impairment of expression and fluorescence of TLR2 and TLR4 in monocytes as well as TLR3 in neutrophils was associated with the manifestations of skin lesions in the patients with DM1 and LN. It is concluded that the measurement of Toll-like receptors in the patient presenting with type 1 diabetes mellitus and lipoid necrobiosis can be used in clinical practice for the prediction of the development of dermatosis.

липоидный некробиозсахарный диабетТолл-подобные рецепторыlipoid necrobiosisdiabetes mellitusToll-like receptorsReferencesХэбиф Т.П. Кожные болезни. Диагностика и лечение. Под общ. ред. А.А. Кубановой. Пер. с англ. 3-е изд. М: МЕД-пресс-информ 2006; 578.Хэбиф Т.П. Кожные болезни. Диагностика и лечение. Под общ. ред. А.А. Кубановой. Пер. с англ. 3-е изд. М: МЕД-пресс-информ 2006; 578.Лезвинская Е.М., Шалаева И.В., Ломовцева О.Б. Клинические и диагностические особенности липоидного некpобиоза. Рос журн кож и вен бол 2000; 4: 22—27.Лезвинская Е.М., Шалаева И.В., Ломовцева О.Б. Клинические и диагностические особенности липоидного некpобиоза. Рос журн кож и вен бол 2000; 4: 22—27.Eisendle K., Zelger B. The expanding spectrum of cutaneous borreliosis. G Ital Dermatol Venereol 2009; 144: 2: 157—171.Eisendle K., Zelger B. The expanding spectrum of cutaneous borreliosis. G Ital Dermatol Venereol 2009; 144: 2: 157—171.Peyri J., Moreno A., Marcoval J. Necrobiosis lipoidica. Semin Cutan Med Surg 2007; 26: 2: 87—89.Peyri J., Moreno A., Marcoval J. Necrobiosis lipoidica. Semin Cutan Med Surg 2007; 26: 2: 87—89.Lai Y., Gallo R.L. Toll-like receptors in skin infections and infl ammatory disease. Infect Dis Drug Targ 2008; 8: 3:144—155.Lai Y., Gallo R.L. Toll-like receptors in skin infections and infl ammatory disease. Infect Dis Drug Targ 2008; 8: 3:144—155.Hirschfeld M., Kirschning C.J., Schwandner R., Wesche H., Weis J.H., Wooten R.M., Weis J.J. Cutting edge: infl ammatory signalling by Borrelia burgdorferi lipoproteins is mediated by tolllike receptor 2. J Immunol 1999; 163: 2382—2386.Hirschfeld M., Kirschning C.J., Schwandner R., Wesche H., Weis J.H., Wooten R.M., Weis J.J. Cutting edge: infl ammatory signalling by Borrelia burgdorferi lipoproteins is mediated by tolllike receptor 2. J Immunol 1999; 163: 2382—2386.Takeuchi O., Hoshino K., Kawai T., Sanjo H., Takada H., Ogawa T., Takeda K., Akira S. Diff erential roles of TLR2 and TLR4 in recognition of gram-negative and gram-positive bacterial cell wall components. Immunity 1999; 11: 443—451.Takeuchi O., Hoshino K., Kawai T., Sanjo H., Takada H., Ogawa T., Takeda K., Akira S. Diff erential roles of TLR2 and TLR4 in recognition of gram-negative and gram-positive bacterial cell wall components. Immunity 1999; 11: 443—451.Muzio M., Bosisio D., Polentarutti N., D’amico G., Stoppacciaro A., Mancinelli R., van’t Veer C., Penton-Rol G., Ruco L.P., Allavena P., Mantovani A. Diff erential expression and regulation of toll-like receptors (TLR) in human leukocytes: selective expression of TLR3 in dendritic cells. J Immunol 2000; 164:5998—6004.Muzio M., Bosisio D., Polentarutti N., D’amico G., Stoppacciaro A., Mancinelli R., van’t Veer C., Penton-Rol G., Ruco L.P., Allavena P., Mantovani A. Diff erential expression and regulation of toll-like receptors (TLR) in human leukocytes: selective expression of TLR3 in dendritic cells. J Immunol 2000; 164:5998—6004.Uehara A., Fujimoto Y., Fukase K., Takada H. Various human epithelial cells express functional Toll-like receptors, NOD1 and NOD2 to produce anti-microbial peptides, but not proinfl ammatory cytokines. Mol Immunol 2007; 44: 12: 3100—3111.Uehara A., Fujimoto Y., Fukase K., Takada H. Various human epithelial cells express functional Toll-like receptors, NOD1 and NOD2 to produce anti-microbial peptides, but not proinfl ammatory cytokines. Mol Immunol 2007; 44: 12: 3100—3111.Alexopoulou L., Holt A.C., Medzhitov R., Flavell R.A. Recognition of double-stranded RNA and activation of NF-kappaB by Tolllike receptor 3. Nature 2001; 413: 732—738.Alexopoulou L., Holt A.C., Medzhitov R., Flavell R.A. Recognition of double-stranded RNA and activation of NF-kappaB by Tolllike receptor 3. Nature 2001; 413: 732—738.Cavassani K.A., Ishii M., Wen H., Schaller M.A., Lincoln P.M., Lukacs N.W., Hogaboam C.M., Kunkel S.L. TLR3 is an endogenous sensor of tissue necrosis during acute infl amatory events. J Exp Med 2008; 205: 11: 2609—2621.Cavassani K.A., Ishii M., Wen H., Schaller M.A., Lincoln P.M., Lukacs N.W., Hogaboam C.M., Kunkel S.L. TLR3 is an endogenous sensor of tissue necrosis during acute infl amatory events. J Exp Med 2008; 205: 11: 2609—2621.Migita K., Miyashita T., Maeda Y., Nakamura M., Yatsuhashi H., Kimura H., Ishibashi H., Eguchi K. Toll-like receptor expression in lupus peripheral blood mononuclear cells. J Rheumatol 2007; 34:3: 493—500.Migita K., Miyashita T., Maeda Y., Nakamura M., Yatsuhashi H., Kimura H., Ishibashi H., Eguchi K. Toll-like receptor expression in lupus peripheral blood mononuclear cells. J Rheumatol 2007; 34:3: 493—500.Orihara K., Nagata K., Hamasaki S., Oba R., Hirai H., Ishida S., Kataoka T., Oketani N., Ogawa M., Mizoguchi E., Ichiki H., Tei C. Time-course of Toll-like receptor 2 expression, as a predictor of recurrence in patients with bacterial infectious diseases. Clin Exp Immunol 2007; 148: 2: 260—270.Orihara K., Nagata K., Hamasaki S., Oba R., Hirai H., Ishida S., Kataoka T., Oketani N., Ogawa M., Mizoguchi E., Ichiki H., Tei C. Time-course of Toll-like receptor 2 expression, as a predictor of recurrence in patients with bacterial infectious diseases. Clin Exp Immunol 2007; 148: 2: 260—270.Carrasco S., Neves F.S., Fonseca M.H., Goncalves C.R., Saad C.G., Sampaio-Barros P.D., Goldenstein-Schainberg C. Toll-like receptor (TLR) 2 is upregulated on peripheral blood monocytes of patients with psoriatic arthritis: a role for a grampositive infl ammatory trigger? Clin Exp Rheumatol 2011; 29: 6: 958—962.Carrasco S., Neves F.S., Fonseca M.H., Goncalves C.R., Saad C.G., Sampaio-Barros P.D., Goldenstein-Schainberg C. Toll-like receptor (TLR) 2 is upregulated on peripheral blood monocytes of patients with psoriatic arthritis: a role for a grampositive infl ammatory trigger? Clin Exp Rheumatol 2011; 29: 6: 958—962.Chang J.H., Hampartzoumian T., Everett B., Lloyd A., McCluskey P.J., Wakefield D. Changes in Toll-like receptor (TLR)-2 and TLR4 expression and function but not polymorphisms are associated with acute anterior uveitis. Invest Ophthalmol Vis Sci 2007; 48: 4: 1711—1717.Chang J.H., Hampartzoumian T., Everett B., Lloyd A., McCluskey P.J., Wakefield D. Changes in Toll-like receptor (TLR)-2 and TLR4 expression and function but not polymorphisms are associated with acute anterior uveitis. Invest Ophthalmol Vis Sci 2007; 48: 4: 1711—1717.Patsatsi A., Kyriakou A., Sotiriadis D. Necrobiosis lipoidica: early diagnosis and treatment with tacrolimus. Case Rep Dermatol 2011; 3: 1: 89—93.Patsatsi A., Kyriakou A., Sotiriadis D. Necrobiosis lipoidica: early diagnosis and treatment with tacrolimus. Case Rep Dermatol 2011; 3: 1: 89—93.Кожные и венерические болезни: Руководство для врачей. 2 т. Под ред. Ю.К. Скрипкина, В.Н. Мордовцева. М: Медицина 1999; 317—326.Кожные и венерические болезни: Руководство для врачей. 2 т. Под ред. Ю.К. Скрипкина, В.Н. Мордовцева. М: Медицина 1999; 317—326.Hawryluk E.B., Izikson L., English J.C.3rd. Non-infectious granulomatous diseases of the skin and their associated systemic diseases: an evidence-based update to important clinical questions. Am J Clin Dermatol 2010; 11: 3: 171—181.Hawryluk E.B., Izikson L., English J.C.3rd. Non-infectious granulomatous diseases of the skin and their associated systemic diseases: an evidence-based update to important clinical questions. Am J Clin Dermatol 2010; 11: 3: 171—181.Дедов И.И., Шестакова М.В. (ред.) Алгоритмы специализированной медицинской помощи больным сахарным диабетом. 5-е изд. М 2011.Дедов И.И., Шестакова М.В. (ред.) Алгоритмы специализированной медицинской помощи больным сахарным диабетом. 5-е изд. М 2011.Бутов Ю.С., Васенова В.Ю., Ильина Т.А., Хрусталева Е.А. Фосфоглив в терапии ряда дерматозов. Русс мед журн 2006; 14: 5: 353—356.Бутов Ю.С., Васенова В.Ю., Ильина Т.А., Хрусталева Е.А. Фосфоглив в терапии ряда дерматозов. Русс мед журн 2006; 14: 5: 353—356.Verrotti A., Chiarelli F., Amerio P., Morgese G. Necrobiosis lipoidica diabeticorum in children and adolescents: a clue for underlying renal and retinal disease. Pediat Dermatol 1995; 12: 3: 220—223.Verrotti A., Chiarelli F., Amerio P., Morgese G. Necrobiosis lipoidica diabeticorum in children and adolescents: a clue for underlying renal and retinal disease. Pediat Dermatol 1995; 12: 3: 220—223.Triantafi lou M., Manukyan M., Mackie A. et al. Lipoteichoic acid and toll-like receptor 2 internalization and targeting to the Golgi are lipid raft-dependent. J Biol Chem 2004; 279: 40882—40889.Triantafi lou M., Manukyan M., Mackie A. et al. Lipoteichoic acid and toll-like receptor 2 internalization and targeting to the Golgi are lipid raft-dependent. J Biol Chem 2004; 279: 40882—40889.Martin P. Wound healing—aiming for perfect skin regeneration. Science 1997;276: 75—81.Martin P. Wound healing—aiming for perfect skin regeneration. Science 1997;276: 75—81.McKay I.A., Leigh I.M. Epidermal cytokines and their roles in cutaneous wound healing. Br J Dermatol 1991; 124: 513—518.McKay I.A., Leigh I.M. Epidermal cytokines and their roles in cutaneous wound healing. Br J Dermatol 1991; 124: 513—518.Lai Y., Di Nardo A., Nakatsuji T., Leichtle A., Yang Y., Cogen A.L., Wu Z.R., Hooper L.V., Schmidt R.R., von Aulock S. Commensal bacteria regulate Toll-like receptor 3-dependent infl ammation after skin injury. Nat Med 2009; 15: 1377—1382.Lai Y., Di Nardo A., Nakatsuji T., Leichtle A., Yang Y., Cogen A.L., Wu Z.R., Hooper L.V., Schmidt R.R., von Aulock S. Commensal bacteria regulate Toll-like receptor 3-dependent infl ammation after skin injury. Nat Med 2009; 15: 1377—1382.Lin Q., Fang D., Fang J., Ren X., Yang X., Wen F., Su S.B. Impaired wound healing with defective expression of chemokines and recruitment of myeloid cells in TLR3-defi cient mice. J Immunol 2011; 186: 6: 3710—3717.Lin Q., Fang D., Fang J., Ren X., Yang X., Wen F., Su S.B. Impaired wound healing with defective expression of chemokines and recruitment of myeloid cells in TLR3-defi cient mice. J Immunol 2011; 186: 6: 3710—3717.

The authors declare that there are no conflicts of interest present.