Diyabetik Sıçan Deri Yara İyileşmesinde Probiyotik Etkisi

Yıl 2022, Cilt: 9 Sayı: 1, 151 - 158, 31.03.2022

Emine Müge Karakayalı , Tuna Önal , Mustafa Öztatlıcı , Rabia Duruşma , Tuğba Çavuşoğlu , Erdoğan Kocamaz , Mehmet İbrahim Tuğlu

https://doi.org/10.34087/cbusbed.1078611

Öz

Giriş ve Amaç: Diyabetik deri yarası kronik, tedavisi zor ve maliyetli bir patolojidir Probiyotikler (PB) yeni ürünler olup barsak mikrobiyotasını düzenleyerek cilt yaralarının iyileşme sürecini olumlu yönde etkilerler. Ancak mekanizmaları bilinmemektedir. Bu çalışmada diyabetik sıçan deri yarasına PB katkısı morfolojik parametreler, oksidatif stres, apoptoz, damarlanma, inflamasyon ve bağ doku açısından mekanizmalar araştırıldı.
Gereç ve Yöntemler: Sıçanlar 50 mg/kg intraperitoneal Streptozotosin kullanılarak diyabetik hale getirildi. Sırt bölgesinde 1x1cm tam kat deri defekti yapıldı ve NBL Probiotic Gold preparatı PB olarak oral gavaj ile uygulandı. Yara iyileşmesinin 7. gününde örnekler alındı. Histokimyasal olarak HE boyamaları ile morfolojik inceleme ve skorlama yapıldı. Örnekler, immünohistokimyasal yöntem ile eNOS, Kaspas 3, IL-10, VEGF ve Kollagen1 ile boyandı ve H-skor ile değerlendirildi.
Bulgular: Tam kat deri defekti ile oluşan yaranın iyileşmesinde PB kullanımı morfometrik skorlamada anlamlı bir hızlanma ve olgunlaşma sağladı. Yara yerinde hasara bağlı oluşan eNOS, Kaspas 3 ve IL-10 artışı ile VEGF ve Kollagen1 azalışının PB ile anlamlı bir şekilde geri döndürüldüğü izlendi.
Sonuç: PB için deride kronik, zor ve maliyetli yara iyileşmesi üzerindeki olumlu etkisinin klinikte hasta yaşam kalitesini arttıracağı düşünülmektedir.

Anahtar Kelimeler

Deneysel Diyabet, Probiyotik, Deri, Yara İyileşmesi, Oksidatif Srres, Apopitoz, Damarlanma

Destekleyen Kurum

Manisa Celal Bayar Üniversitesi Bilimsel Araştırma Projeleri Birim Koordinatörlüğü

Proje Numarası

Proje No: 2020-058

Teşekkür

Desteklerinden dolayı teşekkürederiz

Effect of Probiotics on Diabetic Rat Skin Wound Healing

Öz

Objective: Treatment of diabetic skin wound is a chronic, difficult and expensive pathology. Probiotics (PB) are new products which affects the skin wound healing process positively by regulating the intestinal microbiota. However, the mechanisms are unknown. In this study, the mechanisms of PB contribution to diabetic rat skin wound in terms of morphological parameters, oxidative stress, apoptosis, vascularization, inflammation and connective tissue were investigated.
Materials and Methods: Rats were made diabetic using 50 mg/kg intraperitoneal Streptozotocin. A 1x1cm full-thickness skin defect was made in the back area and NBL Probiotic Gold preparation was applied as PB by oral gavage. Samples were obtained on the 7th day of wound healing. Morphological examination and scoring were performed by histochemical HE and MT staining. The samples were stained with eNOS, Caspas 3, IL-10, VEGF and Collagen1 by immunohistochemistry and evaluated with H-score.
Results: The effect of PB in the healing of the wound formed by a full-thickness skin defect provided a significant acceleration and maturation in morphometric scoring. It was observed that the increase in eNOS, Kaspas 3 and IL-10, and the decrease in VEGF and Collagen1 due to damage at the wound site were significantly reversed by PB.
Conclusion: It was thought that the positive effect of PB on chronic, difficult and costly wound healing in the skin would increase the quality of life of the patients in the clinic.

Anahtar Kelimeler

Experimental Diabetes, Probiotic, Wound Healing, Oksidative stress, Apoptosis, Vascularization

Proje Numarası

Proje No: 2020-058

Kaynakça

• 1.Tsiouris CG, Kelesi M, Vasilopoulos G, Kalemikerakis I, Papageorgiou EG. The efficacy of probiotics as pharmacological treatment of cutaneous wounds: Meta-analysis of animal studies. Eur J Pharm Sci. 2017; 104:230–239.
• 2. Johnson TR, Gómez BI, McIntyre MK, et al. The Cutaneous Microbiome and Wounds: New Molecular Targets to Promote Wound Healing. Int J Mol Sci. 2018;19(9):2699.
• 3. Ponugoti B, Xu F, Zhang C, Tian C, Pacios S, Graves DT. FOXO1 promotes wound healing through the up-regulation of TGF-β1 and prevention of oxidative stress. J Cell Biol. 2013 Oct 28;203(2):327-43.
• 4.Satish Patel, Shikha Srivastava, Manju Rawat Singh, Deependra Singh, Mechanistic insight into diabetic wounds: Pathogenesis, molecular targets and treatment strategies to pace wound healing, Biomedicine & Pharmacotherapy, 2019 Volume 112, 108615, ISSN 0753-3322, https://doi.org/10.1016/j.biopha.2019.108615.
• 5. Tan, J.L., Lash, B., Karami, R. et al. Restoration of the healing microenvironment in diabetic wounds with matrix-binding IL-1 receptor antagonist. Commun Biol 2021: 4, 422.
• 6.Fijan S, Frauwallner A, Langerholc T, et al. Efficacy of Using Probiotics with Antagonistic Activity against Pathogens of Wound Infections: An Integrative Review of Literature. Biomed Res Int. 2019; 2019:7585486.
• 7.Yu Y, Dunaway S, Champer J, Kim J, Alikhan A. Changing our microbiome: probiotics in dermatology. Br J Dermatol. 2020;182(1):39–46.
• 8.Campos LF, Tagliari E, Casagrande TAC, Noronha L, Campos ACL, Matias JEF. Effects Of Probıotıcs Supplementatıon On Skın Wound Healıng In Dıabetıc Rats. Arq Bras Cir Dig. 2020: 8;33(1): e1498.
• 9.Drago F, Gariazzo L, Cioni M, Trave I, Parodi A. The microbiome and its relevance in complex wounds. Eur J Dermatol. 2019: 1;29(1):6-13.
• 10.He Zhou, Xue Zhao, Lin Sun, Yujia Liu, You Lv, Xiaokun Gang, Guixia Wang, "Gut Microbiota Profile in Patients with Type 1 Diabetes Based on 16S rRNA Gene Sequencing: A Systematic Review,Disease Markers, vol. 2020,
• 11. Gürpınar, T., Ekerbiçer, N., Uysal, N., Barut, T., Tarakçı, F., & Tuglu, M. I. 2012. The effects of the melatonin treatment on the oxidative stress and apoptosis in diabetic eye and brain. The Scientific World J. https://doi.org/10.1100/2012/498489
• 12. Ebaid, H., Abdel-salam, B., Hassan, I. et al. Camel milk peptide improves wound healing in diabetic rats by orchestrating the redox status and immune response. Lipids Health Dis 2015:14, 132.
• 13. Akhoundzadeh K, Vakili A, Shadnoush M, Sadeghzadeh J. Effects of the Oral Ingestion of Probiotics on Brain Damage in a Transient Model of Focal Cerebral Ischemia in Mice. Iran J Med Sci. 2018 Jan;43(1):32-40.
• 14. Beyhan G, Yücel B. Koca, Mahmud Ö., MI Tuğlu, Matrix changes due to the toxic effects of metronidazole in intestinal tissue of fish (Onchorhynchus mykiss), Chemosphere, 2016:44; Pp. 1605-1610.
• 15. I Aydemir, MM Özkut, F Fırat, A Gümürüdü, DH Sal, K Erdoğan, A Göker, Effects of stem cells applications on oxidative stress and apoptosis during implantation. Asian Pacific Journal of Reproduction 2019:7 (5), 229.
• 16. Birinci H., Halıcıoğlu BŞ., Öztatlıcı M., Yüncü M. Sisplatinin Neden Olduğu Nefrotoksisite ve Ultrastrüktürel Hasar Üzerine Kurkuminin Koruyucu Etkisi. Celal Bayar Üniversitesi Sağlık Bilimleri Enstitüsü Dergisi 2021: 8; 4, 598- 605.
• 17.-BA Altan, O Sokucu, MM Ozkut. , S Inan and histological investigation of the effects of low-level laser therapy on orthodontic tooth movement Lasers in medical science 2012:27 (1), 131-140.
• 18. Öztürk Ş.,Ceyda L.,Öztürk Ş.,(2021)Deneysel Karaciğer Rezeksiyonu Oluşturulmuş Ratlarda Rejenerasyon ve Apoptozun Değerlendirilmesi. Celal Bayar Üniversitesi Sağlık Bilimleri Enstitüsü Dergisi, 2021:8,; 4, 2021, 621 – 626.
• 19. Busra SEN , Mehmet İbrahim TUĞLU , (2020),Farklı İki Yöntemle Oluşturulan Deneysel Prematür Over Yetmezlik Modelinde Overlerin Histopatolojik Değerlendirilmesi. Celal Bayar Üniversitesi Sağlık Bilimleri Enstitüsü Dergisi, Cilt 7, Sayı 3, 2020, 257- 265.
• 20. Halicioglu SB, KASM S., Tuglu MI. The relationship of 4-vinylcyclohexene diepoxide toxicity with cell death, oxidative stress, and gap junctions in female rat ovaries. Reprod Med Biol. 2021;20(4):543-553.
• 21.Ibrahim, K. S., Bourwis, N., Dolan, S., Lang, S., Spencer, J., & Craft, J. A. Characterisation of gut microbiota of obesity and type 2 diabetes in a rodent model. Bioscience of microbiota, food and health, 2021: 40(1), 65–74.
• 22.Liling Deng, Chenzhen Du, Peiyang Song, Tianyi Chen, Shunli Rui, David G. Armstrong, and Wuquan Deng Published The Role of Oxidative Stress and Antioxidants in Diabetic Wound Healing Oxid Med Cell Longev. 2021: 4;8852759
• 23.Asghari M, Kanonisabet A, Safakhah M, Azimzadeh Z, Mostafavinia A, Taheri S,Amini A, Ghorishi SK, JalaliFiroozkohi R, Bayat S, Bayat M. The effect of combined photobiomodulation and metformin on open skin wound healing in a non-genetic model of type II diabetes. J Photochem Photobiol B. 2017; 169:63-69.
• 24.Blair MJ, Jones JD, Woessner AE, Quinn KP. Skin Structure-Function Relationships and the Wound Healing Response to Intrinsic Aging. Adv Wound Care (New Rochelle. 2020: 1;9(3):127-143.
• 25.Campos LF, Tagliari E, Casagrande TAC, Noronha L, Campos ACL, Matias JEF. Effects Of Probıotıcs Supplementatıon On Skın Wound Healıng In Dıabetıc Rats. Arq Bras Cir Dig. 2020: 8;33(1): e1498.
• 26.Tagliari E, Campos LF, Casagrande TAC, Fuchs T, de Noronha L, Campos ACL. Effects of oral probiotics administration on the expression of transforming growth factor β and the proinflammatory cytokines interleukin 6, interleukin 17, and tumor necrosis factor α in skin wounds in rats. JPEN J Parenter Enteral Nutr. 2021: 26.
• 27.Tagliari E, Campos LF, Campos AC, Costa-Casagrande TA, Noronha L. Effect Of Probıotıc Oral Admınıstratıon On Skın Wound Healıng In Rats. Arq Bras Cir Dig. 2019:9;32(3): e1457.
• 28.Gardiner M, Vicaretti M, Sparks J, Bansal S, Bush S, Liu M, Darling A, Harry E, Burke CM. A longitudinal study of the diabetic skin and wound microbiome. PeerJ. 2017: 20;5: e3543.
• 29.Drago F, Gariazzo L, Cioni M, Trave I, Parodi A. The microbiome and its relevance in complex wounds. Eur J Dermatol. 2019 Feb 1;29(1):6-13.
• 30. Mohseni AH, Casolaro V, Bermúdez-Humarán LG, Keyvani H, Taghinezhad-S S. Modulation of the PI3K/Akt/mTOR signaling pathway by probiotics as a fruitful target for orchestrating the immune response. Gut Microbes. 2021 ;13(1):1-17.
• 31. Liling Deng, Chenzhen Du, Peiyang Song, Tianyi Chen, Shunli Rui, David G. Armstrong, and Wuquan Deng Published The Role of Oxidative Stress and Antioxidants in Diabetic Wound Healing Oxid Med Cell Longev. 2021:4;8852759.
• 32.Honnegowda TM, Kumar P, Udupa EGP., Kumar S., Kumar U., Rao P. Role of angiogenesis and angiogenic factors in acute and chronic wound healing. Plast Aesthet Res 2015; 2:243-9.
• 33.Fijan S, Frauwallner A, Langerholc T, et al. Efficacy of Using Probiotics with Antagonistic Activity against Pathogens of Wound Infections: An Integrative Review of Literature. Biomed Res Int. 2019:7585486. Published 2019: 12.
• 34.He Zhou, Xue Zhao, Lin Sun, Yujia Liu, You Lv, Xiaokun Gang, Guixia Wang, "Gut Microbiota Profile in Patients with Type 1 Diabetes Based on 16S rRNA Gene Sequencing: A Systematic Review",Disease Markers, vol. 2020, Article ID 3936247, p11.
• 35.Ibrahim, K. S., Bourwis, N., Dolan, S., Lang, S., Spencer, J., & Craft, J. A. (2021). Characterisation of gut microbiota of obesity and type 2 diabetes in a rodent model. Bioscience of microbiota, food and health, 40(1), 65–74.
• 36.Jere SW, Houreld NN, Abrahamse H. Role of the PI3K/AKT (mTOR and GSK3β) signalling pathway andphotobiomodulation in diabetic wound healing. Cytokine Growth Factor Rev. 2019; 50:52-59.
• 37.Johnson TR, Gómez BI, McIntyre MK, et al. The Cutaneous Microbiome and Wounds: New Molecular Targets to Promote Wound Healing. Int J Mol Sci. 2018;19(9):2699.