Hiperbarik Oksijen Tedavisinin, Diyabetik Ayak Yarası Olan Hastalarda Hipoksiyle İndüklenen Faktör-1α, İndüklenebilir Nitrik Oksit Sentaz ve Vasküler Endotelyal Büyüme Faktörü Seviyeleri Üzerine Etkisi

Yıl 2019, Cilt: 6 Sayı: 3, 142 - 146, 31.12.2019

Serkan Ergözen , Hakan Ay

Öz

Hiperbarik oksijen
tedavisinin (HBOT) hipoksik yara ortamını düzelterek yara iyileşmesine katkıda
bulunduğu birçok çalışmayla kanıtlanmıştır. Ancak yara bölgesinde arttırılan
oksijenin hangi mekanizmalarla yara iyileşmesine katkıda bulunduğu halen
aydınlatılmaya çalışılan bir konudur. Bu çalışma diyabetik ayak iyileşmesinde
etkisi olduğunu düşündüğümüz hipoksiyle indüklenen faktör-1α (HIF-1α),
indüklenebilir nitrik oksit sentaz (iNOS) ve vasküler endotelyal büyüme faktörü
(VEGF) seviyeleri üzerine HBOT’ nin etkilerini araştırmayı amaçlamıştır.
Çalışmaya Wagner sınıflaması evre 2-3 ve 4 diyabetik ayak yarası olan 20 hasta
dahil edilmiştir. Hastaların yaralarından küretajla ilk HBOT seansı öncesi ve
10. seans sonrası doku örnekleri alınmış ve -82 °C’ de saklanmıştır. Tüm
örnekler toplandıktan sonra, bahsedilen parametrelerin ekspresyonları polimeraz
zincir reaksiyonu çalışmasıyla değerlendirilmiştir. Sonuçlar HIF1-α’ daki
artışın, iNOS ve VEGF’ deki artışla anlamlı korelasyonu olduğunu göstermiştir
(p<0.05). Majör ve minor amputasyona giden hastalarda VEGF, iNOS ve HIF1-α
seviyeleri artarken iyileşen hastalarda tüm parametreler düşüş göstermiştir, ki
bu farklar istatistiksel olarak anlamsız bulunmuştur. Bu verilere göre HBOT’
nin uzamış hipoksik stimulusu inhibe ettiği ve bahsedilen parametrelerin
seviyeleri ile bunların uzamış ve yoğun ekspresyonlarının yara iyileşmesi
üzerindeki olumsuz etkilerini azalttığı sonucuna vardık.

Anahtar Kelimeler

Diyabetik Ayak, Hiperbarik Oksijen, Hipoksiyle İndüklenen Faktör, Yara İyileşmesi

The Effects of Hyperbaric Oxygen Treatment on Hypoxia Inducible Factor-1α, Inducible Nitric Oxide Synthase and Vascular Endothelial Growth Factor Levels in Patients with Diabetic Foot Wound

Öz

A number of studies
have proved that hyperbaric oxygen therapy (HBOT) contributes to wound healing
by improving hypoxic wound site. However, the mechanisms, by which the enhanced
oxygen in the wound site contributes to wound healing, still remain to be
elucidated. This study aimed to investigate the effects of the HBOT on hypoxia
inducible factor-1α (HIF-1α), inducible nitric oxide synthase (iNOS) and
vascular endothelial growth factor (VEGF) levels that we consider influential
on diabetic foot healing. 20 patients were included in the study with diabetic
foot wounds of Wagner classification grade 2-3 and 4. Tissue samples from the
patients’ wounds were taken before the first HBOT session and after the 10th
session by curettage and stored at -82 °C. Upon collection of all samples,
expressions of the stated parameters were examined through polymerase chain
reaction (PCR) study. The results revealed that the increase in HIF1-α has a
meaningful correlation with the increase in iNOS and VEGF (p<0.05). VEGF,
iNOS and HIF1-α levels in patients who underwent major or minor amputations
went up; while all parameters in patients who recovered indicated decline which
is statistically non-significant. According to these data, we concluded that
HBOT inhibited prolonged hypoxic stimulus and decreased both the levels of the
mentioned parameters and the negative effects of prolonged and intense
expressions of them on wound healing.

Anahtar Kelimeler

Diabetic Foot, Hyperbaric Oxygen, Hypoxia Inducible Factor, Wound Healing

Kaynakça

• 1. Palumbo PJ, Melton LJI. Peripheral vascular disease and diabetes. In National Diabetes Data Group (ed): Diabetes In America (NIH publ. no. 495-1468). 1995; 401-8. 2nd ed. Washington, DC, US. Government Printing Office.
• 2. Semenza GL. Perspectives on oxygen sensing. Cell. 1999;98(3):281-4.
• 3. Semenza GL. Hypoxia-inducible factor 1 and the molecular physiology of oxygen homeostasis. J Lab Clin Med. 1998;131(3):207-14.
• 4. Zhang Q, Chang Q, Cox RA, Gong X, Gould LJ. Hyperbaric oxygen attenuates apoptosis and decreases inflammation in an ishemic wound model. J Invest Dermatol. 2008;128(8):2102-12.
• 5. Halterman MW, Federoff HJ. HIF-1alpha and p53 promote hypoxia-induced delayed neuronal death in models of CNS ischemia. Exp Neurol. 1999;159(1):65-72.
• 6. Calvert JW, Cahil J, Yamaguchi-Okada M, Zhang JH. Oxygen treatment after experimental hypoxia-ischemia in neonatal rats alters the expression of HIF-1α and its downstream target genes. J Appl Physiol (1985). 2006;101(3):853-65.
• 7. Palmer LA, Semenza GL, Stoler MH, Johns RA. Hypoxia induces type II NOS gene expression in pulmonary artery endothelial cells via HIF-1. Am J Physiol. 1998;274(2 Pt 1):L212-9.
• 8. McCormick CC, Li WP, Calero M. Oxygen tension limits nitric oxide synthesis by activated macrophages. Biochem J. 2000;350(Pt 3):709-16.
• 9. Wiesener MS, Maxwell PH. HIF and oxygen sensing; as important to life as the air we breathe?. Ann Med. 2003;35(3):183-90.
• 10. Kang TS, Gorti GK, Quan SY, Ho M, Koch RJ. Effect of hyperbaric oxygen on the growth factor profile of fibroblasts. Arch Facial Plast Surg. 2004;6(1):31-5.
• 11. Gajendrareddy PK, Sen CK, Horan MP, Marucha, PT. Hyperbaric oxygen therapy ameliorates stres-impaired dermal wound healing. Brain Behav and Immun. 2005;19(3): 217-22.
• 12. Jude EB, Boulton AJ, Ferguson MW, Appleton I. The role of nitric oxide synthase isoforms and arginase in the pathogenesis of diabetic foot ulcers: possible modulatory effects by transforming growth factor beta 1. Diabetologia. 1999;42(6):748-57.
• 13. Yamasaki K, Edington HD, McClosky C et al. Reversal of impaired wound repair in iNOS-deficient mice by topical adenoviral-mediated iNOS gene transfer. J Clin Invest. 1998;101(5): 967-71.
• 14. Schäffer MR, Tantry U, Thornton FJ, Barbul A. Inhibition of nitric oxide synthesis in wounds: pharmacology and effect on accumulation of collogen in wounds in mice. Eur J Surg. 1999;165(3):262-7.
• 15. Schäffer MR, Efron PA, Thornton FJ, Klingel K, Gross SS, Barbul A. Nitric oxide, an autocrine regulator of wound fibroblast synthetic function. J Immunol. 1997;158(5):2375-81.
• 16. Schäffer MR, Tantry U, Efron PA, Ahrendt GM, Wasserkrug HL, Barbul A. Diabetes-impaired wound healing and reduced wound nitric oxide synthesis: a possible pathophysiologic correlation. Surgery. 1997;121(5):513-9.
• 17. Schäffer MR, Tantry U, Ahrendt GM, Wasserkrug HL, Barbul A. Acute protein-calorie malnutrition impairs wound healing: a possible role of decreased wound nitric oxide synthesis. J Am Coll Surg. 1997;184(1):37-43.
• 18. Cross RK, Wilson KT. Nitric oxide in inflammatory bowel disease. Inflamm Bowel Dis. 2003;9(3):179-89.
• 19. Takahashi T. Pathophysiological significance of neuronal nitric oxide synthase in the gastrointestinal tract. J Gastroenterol. 2003;38(5):421-30.
• 20. Sheikh AY, Gibson JJ, Rollins MD, Hopf HW, Hussain Z, Hunt TK. Effect of hyperoxia on vascular endothelial growth factor levels in a wound model. Arch Surg. 2000;135(11):1293-7.
• 21. Shenberger JS, Zhang L, Powell RJ, Barchowsky A. Hyperoxia enhances VEGF release from A549 cells via post-transcriptional processes. Free Radic Biol Med. 2007;43(5):844-52.
• 22. Zhang M, Liu S, Guan E et al. Hyperbaric oxygen therapy can ameliorate the EMT phenomenon in keloid tissue. Medicine (Baltimore). 2018; 97(29):e11529.
• 23. Lu Z, Ma J, Liu B et al. Hyperbaric oxygen therapy sensitizes nimustine treatment for glioma in mice. Cancer Med. 2016; 5(11):3147-55.