İntestinal İskemi/Reperfüzyon Modelinde Tiroid Hormon Ön Koşullanmasının İnce Bağırsak ve Akciğer Hasarı Üzerine Etkisi
Çeşitli deneysel çalışmalarda l-3,3′,5- triiodotronin (T3) veya ltiroksin
(T4) önkoşullanmasının karaciğer, beyin, kalp ve böbrek
iskemi reperfüzyon (İ/R) hasarına karşı koruyucu etkili olduğu
gösterilmiştir. İntestinal I/R hasarı, genellikle şok, akut mezenterik
iskemi, sepsis, mezenterik tromboz veya bağırsak nakli gibi birçok
klinik durumun neden olduğu kritik bir tablodur. Bu çalışmanın
amacı T3 ile oluşturulan önkoşullanmanın intestinal İ/R ile oluşan
ince bağırsak ve akciğer dokusundaki hasara karşı olası koruyucu
etkisini incelemektir.
Erkek Wistar Albino cinsi sıçanlara 30 dakika mezenterik iskemi ve
sonrasında 3 saat reperfüzyon uygulandı. Her grupta 8 hayvan olmak
üzere 4 gruba ayrıldılar: sham kontrol, İ/R kontrol, İ/R +50µg/kg T3
uygulanan ve İ/R+100µg/kg T3 uygulanan grup. İntestinal ve
akciğer dokusundaki hasar histopatolojik olarak incelenmiştir.
Sonuçlarımız ince bağırsak ve akciğer dokusunda 100 µg/kg
dozunda T3 önkoşullanmasının İ/R ile oluşan patolojik değişikleri
azalttığını göstermektedir. İ/R grubunda hem akciğer hem de
intestinal dokuda histopatolojik hasar değerlendirmesinin yüksek
seviyesinde olduğu bulunmuştur. 100 µg İ/R +T3 uygulanan grupta
intestinal mukoza ve akciğer hasarının İ/R ve İ/R +50µg T3
uygulanan gruba göre düşük olduğu saptanmıştır.
Sonuç olarak, intestinal I/R hasarından önce T3 ile oluşturulan
önkoşullanmanın bağırsak iskemisinin neden olduğu ince bağırsak
ve akciğer dokusu üzerinde histopatolojik olarak koruyucu etkili
olduğu gözlemlendi.
Effect of Thyroid Hormone Pre-conditioning on Intestinal and Lung Damage in The Intestinal Ischemia/Reperfusion Model
Pre-conditioning of 1-3,3 ', 5-triiodothronine (T3) or 1-tyroxine (T4)
in various experimental studies has been shown to be protective
against hepatic, brain, cardiac and renal ischemia reperfusion (I/R)
damage. Intestinal I/R injury, a critical condition usually caused by
many clinical scenarios such as shock, acute mesenteric ischemia,
sepsis, mesenteric thrombosis, or bowel transplantation. The purpose
of this study is to examine the possible protective effect of
preconditioning with T3 against damage to the small intestine and
lung tissue caused by intestinal I / R.
Male Wistar Albino rats were subjected to mesenteric ischemia (30
min) followed by reperfusion (3h). Four groups were designed, each
of contain 8 animals: sham control; I/R control; I/R +50µg/kg T3
administration; and I/R+100µg/kg T3 administration. Intestinal and
lung tissue damage was examined histopathologically.
Our results indicate that 100 µg/kg T3 preconditioning attenuates the
I/R-induced histopathological changes in intestinal and lung tissues.
Histopathological damage assessment in both lung and intestinal
tissue was found to be high in the I/R group. In the 100µg T3 treated
group, intestinal mucosa and lung injury were found to be lower than
I / R and 50µg T3 treated groups.
In conclusion, it was observed that T3-induced preconditioning
before intestinal I/R injury was histopathologically protective effect
on small intestine and lung tissue caused by intesinal ischemia.
___
- 1. Zhu Q, He G, Wang J, Wang Y, Chen W, Guo T.
Down-regulation of toll-like receptor 4 alleviates
intestinal ischemia reperfusion injury and acute lung
injury in mice. Oncotarget 2017;8(8):13678-13689.
- 2.Taha MO, Miranda-Ferreira R, Chang AC,
Rodrigues AM, Fonseca IS, Toral LB, Cardoso MR,
Simões MJ, Oliveira-Junior IS, Monteiro HP,
Fagundes DJ, Taha NS, Caricati-Neto A. Effect of
ischemic preconditioning on injuries caused by
ischemia and reperfusion in rat intestine. Transplant
Proc 2012;44(8):2304-8.
- 3. Sayan-Ozacmak H, Ozacmak VH, Turan I, Barut
F, Hanci V. Pretreatment with remifentanil protects
against the reduced-intestinal contractility related to
the ischemia and reperfusion injury in rat. Braz J
Anesthesiol 2015;65(6):483-90.
- 4. Zhang F, Tong L, Qiao H, Dong X, Qiao G, Jiang
H, Sun X. Taurine attenuates multiple organ injury
induced by intestinal ischemia reperfusion in rats. J
Surg Res 2008;149:101-9.
- 5. He Y, Ye ZQ, Li X, Zhu GS, Liu Y, Yao WF, Luo
GJ. Alpha7 nicotinic acetylcholine receptor
activation attenuated intestine-derived acute lung
injury. J Surg Res 2016; 201(2):258-65.
- 6. Xiong LL, Tan Y, Ma HY, Dai P, Qin YX, Yang
RA, Xu YY, Deng Z, Zhao W, Xia QJ, Wang TH,
Zhang YH. Administration of SB239063, a potent
p38 MAPK inhibitor, alleviates acute lung injury
induced by intestinal ischemia reperfusion in rats
associated with AQP4 downregulation. Int
Immunopharmacol 2016;38:54-60.
- 7. Tian XF, Yao JH, Li YH, Zhang XS, Feng BA,
Yang CM, Zheng SS. Effect of nuclear factor kappa
B on intercellular adhesion molecule-1 expression
and neutrophil infiltration in lung injury induced by
intestinal ischemia/reperfusion in rats. World J
Gastroenterol 2006; 12(3):388-92.
- 8. Jaeschke H. Role of reactive oxygen species in
hepatic ischemia-reperfusion injury and
preconditioning. J Invest Surg 2003;16:127-40.
- 9. Madesh M, Hajnoczky G. VDAC-dependent
permeabilization of the outer mitochondrial
membrane by superoxide induces rapid and massive
cytochrome C release. J Cell Biol 2001; 155:1003-
15.
- 10. Kim SM, Kim SW, Jung YJ, Min SI, Min SK,
Kim SJ, Ha J. Preconditioning with thyroid hormone
(3,5,3-triiodothyronine) prevents renal ischemiareperfusion
injury in mice. Surgery
2014;155(3):554-61.
- 11. Li F, Lu S, Zhu R, Zhou Z, Ma L, Cai L, Liu Z.
Heme oxygenase-1 is induced by thyroid hormone
and involved in thyroid hormone preconditioninginduced
protection against renal warm ischemia in
rat. Mol Cell Endocrinol 2011;339(1-2):54-62.
- 12. Tapia G1, Santibáñez C, Farías J, Fuenzalida G,
Varela P, Videla LA, Fernández V. Kupffer-cell
activity is essential for thyroid hormone rat liver
preconditioning. Mol. Cell. Endocrinol 2010;323
(2):292–297.
- 13. Taki-Eldin A, Zhou L, Xie HY, Chen KJ, Yu D,
He Y, Zheng SS. Triiodothyronine attenuates hepatic
ischemia/reperfusion injury in a partial hepatectomy
model through inhibition of proinflammatory
cytokines, transcription factors, and adhesion
molecules. J Surg Res 2012;178(2):646-56.
- 14. Pantos C, Malliopoulou V, Mourouzis I,
Thempeyioti A, Paizis I, Dimopoulos A, Saranteas
T, Xinaris C, Cokkinos DV. Hyperthyroid hearts
display a phenotype of cardioprotection against
ischemic stress: a possible involvement of heat
shock protein 70. Horm Metab Res 2006;38
(5):308–31.
- 15. Genovese T, Impellizzeri D, Ahmad A,
Cornelius C, Campolo M, Cuzzocrea S, Esposito E.
Post-ischaemic thyroid hormone treatment in a rat
model of acute stroke. Brain Res 2013; 1513:92-102.
- 16. Pirat A, Zeyneloglu P, Aldemir D, Yücel M,
Ozen O, Candan S, Arslan G. Pretreatment with
simvastatin reduces lung injury related to intestinal
ischemia-reperfusion in rats. Anesth Analg
2006;102(1):225-32.
- 17. Hierholzer C, Kalff JC, Audolfsson G, Billiar
TR, Tweardy DJ, Bauer AJ. Molecular and
functional contractile sequelae of rat intestinal
ischemia/reperfusion injury. Transplantation
1999;68(9):1244-54.
- 18. Fantozzi ET, Breithaupt-Faloppa AC, Ricardoda-Silva
FY, Rodrigues-Garbin S, Romero DC, da
Silva Rodrigues A, Riffo-Vasquez Y, Tavares-deLima
W. Estradiol mediates the long-lasting lung
inflammation induced by intestinal ischemia and
reperfusion. J Surg Res 2018;221:1-7.
- 19. Bonservizi WG, Koike MK, Saurim R, Felix GA,
da Silva SM, Montero EF, Taha MO. Ischemic
preconditioning and atenolol on lung injury after
intestinal ischemia and reperfusion in rats.
Transplant Proc 2014;46(6):1862-6.
- 20. Han X, Yao W, Liu Z, Li H, Zhang ZJ, Hei Z,
Xia Z. Lipoxin A4 Preconditioning Attenuates
Intestinal Ischemia Reperfusion Injury through
Keap1/Nrf2 Pathway in a Lipoxin A4 Receptor
Independent Manner. Oxid Med Cell Longev
2016;2016:1-12.
- 21. Oliveira TRR, Oliveira GF, Simões RS, Feitosa
SM, Tikazawa EH, Monteiro HP, Fagundes DJ,
Taha MO. The expression of endothelial and
inducible nitric oxide synthase and apoptosis in
intestinal ischemia and reperfusion injury under the
action of ischemic preconditioning and
pentoxifylline. Acta Cir Bras 2017;32(11):935-948.
- 22. Wang Z, Ji Y, Wang S, Wang R, Li Z, Kang A,
Xu H, Shi M, Zhao M. Protective effect of intestinal
ischemic preconditioning on ischemia reperfusioncaused
lung injury in rats. Inflammation
2015;38(1):424-32.
- 23. Xue TM, Tao LD, Zhang J, Xue TM, Tao LD,
Zhang J, Zhang PJ, Liu X, Chen GF, ZHU, YJ.
Intestinal ischemic preconditioning reduces liver
ischemia reperfusion injury in rats. Mol Med Rep.
2016;13(3):2511-7.
- 24. Ji YY, Wang ZD, Wang SF, Wang BT, Yang ZA,
Zhou XR, Lei NN, Yue WN. Ischemic
preconditioning ameliorates intestinal injury
induced by ischemia-reperfusion in rats. World J
Gastroenterol 2015;21:8081-8.
- 25. Fernández V, Castillo I, Tapia G, Romanque P,
Uribe-Echevarría S, Uribe M, Cartier-Ugarte D.
Thyroid hormone preconditioning: Protection
against ischemia-reperfusion liver injury in the rat.
Hepatology 2007;45:170-177.
- 26. Vargas R, Videla LA. Thyroid hormone
suppresses ischemia-reperfusion-induced liver
NLRP3 inflammasome activation: Role of AMPactivated
protein kinase. Immunol Lett 2017;184:92-
97