DENEYSEL KOLİT MODELİNDE KARACİĞER VE PANKREASTA GÖRÜLEN MORFOMETRİK DEĞİŞİKLİKLER VE VAGAL STİMULASYONUN KRONİK DÖNEMDE BU DEĞİŞİKLİKLER ÜZERİNE OLAN ETKİLERİNİN İNCELENMESİ

Yıl 2024, Cilt: 5 Sayı: 1, 16 - 23, 31.05.2024

Özgenur Koçak Rabet Gozil Kerem Atalar Saadet Özen Akarca Dizakar Ece Alım Ayşe Soylu Meltem Bahcelıoglu

Öz

Giriş: İnflamatuvar bağırsak hastalığı, sindirim sisteminin kronik ve idiyopatik bir hastalığıdır. Hastalık ayrıca karaciğeri ve pankreası da etkilemektedir. Çalışmadaki amacımız transkutanoz aurikular vagal sinir stimulasyonunun (TAVNS) karaciğer ve pankreas hasarının iyileşmesi üzerindeki etkisini incelemektir.

Materyal ve Metot: Çalışmamız 4 grup halinde 36 sıçanla yapılmıştır. Sham grubuna intrakolonik salin enjeksiyonu yapılmış ve TAVNS uygulanmamıştır. Sham+ TAVNS grubuna intrakolonik olarak salin enjekte edilmiş ve TAVNS uygulanmıştır. TNBS+Sham grubuna intrakolonik olarak TNBS (trinitrobenzen sülfonik asit) enjekte edilmiş ve TAVNS uygulanmamıştır. TNBS+TAVNS grubuna hem TNBS enjekte edilmiş hem de TAVNS uygulanmıştır. Karaciğer dokusu ve pankreas dokusu histolojik ve histomorfometrik olarak incelenmiştir.

Bulgular: Çalışmamızda TNBS+Sham ve TNBS+TAVNS gruplarının son vücut ağırlıkları Sham ve Sham+TAVNS gruplarına göre anlamlı olarak düşük bulundu. TNBS uygulanan grupların karaciğer ve pankreas histopatolojik skorları anlamlı olarak yüksekti. TNBS+Sham grubundaki sıçanların karaciğer hepatositlerinde bazı bölgelerde nekrotik alanlar, vakuolar dejenerasyon ve sinüzoidal konjesyon gözlendi. Grup TNBS+TAVNS grubunun karaciğer kesitlerindeki dejeneratif bulgular kısmen azaldı. TNBS+Sham ve TNBS+TAVNS gruplarındaki hayvanların pankreasındaki Langerhans adacıklarının sayısı ve alanı, Sham ve Sham+ TAVNS gruplarına göre daha düşük bulundu.

Sonuç: Bu çalışmada sıçanlarda TNBS kaynaklı kolitin karaciğer ve pankreasta histopatolojik ve histomorfometrik değişikliklere neden olarak kilo kaybına yol açtığı ve TAVNS'nun bu değişiklikler üzerinde terapötik etkilerinin olduğu tespit edilmiştir.

Anahtar Kelimeler

kolit, vagal sinir stimulasyonu, karaciğer, pankreas

Proje Numarası

TTU-2021-7301

Morphometric Changes in Liver and Pancreas in Experimental Colitis Model and Examination of the Effects of Vagal Stimulation on These Changes in Chronic Period

Öz

Introduction: Inflammatory bowel disease is a chronic and idiopathic disease of the digestive tract. The disease also affects the liver and pancreas. Our aim in the study was to examine the effect of transcutaneous auricular vagal nerve stimulation (TAVNS) on the healing of liver and pancreas damage.

Material and Method: 36 rats in 4 groups were included in this study. The Sham group was intracolonic injected with saline and TAVNS was not applied. The Sham+ TAVNS group was injected intracolonically with saline and TAVNS was applied. The TNBS+Sham group was injected with TNBS (trinitrobenzene sulfonic acid) intracolonically and TAVNS was not applied. In TNBS+ TAVNS group both TNBS was injected and TAVNS was applied. Liver tissue and pancreas tissue were examined histologically and histomorphometrically.

Results: In our study, the final body weights of TNBS+Sham and TNBS+ TAVNS groups were found to be significantly lower than sham and Sham+TAVNS groups. The liver and pancreas histopathological scores of the TNBS injected groups were significantly higher. In the liver hepatocytes of rats in TNBS+Sham group, necrotic areas, vacuolar degeneration, and sinusoidal congestion were observed in some regions. Degenerative findings in liver sections of group TNBS+ TAVNS group were also partially reduced. The number and area of Langerhans islets in the pancreas of the animals in TNBS+Sham and TNBS+ TAVNS groups were found to be lower than in Sham and Sham+ TAVNS groups.

Conclusions: In this study, we found that TNBS-induced colitis in rats caused histopathological and histomorphometric changes in the liver and pancreas, causing weight loss, and that TAVNS had therapeutic effects on these changes.

Anahtar Kelimeler

colitis, vagal nerve stimulation, liver, pancreas

Etik Beyan

Ethical approval of the study was obtained from the Animal Research Committee at Ankara Gazi University (G.Ü.ET 21.041).

Destekleyen Kurum

The study was supported by Gazi University Scientific Research Projects Unit with project number TTU-2021-7301.

Proje Numarası

TTU-2021-7301

Teşekkür

We extend our thanks to Gazi University and Yüksek İhtisas University.

Kaynakça

• 1. Baron JH. Inflammatory bowel disease up to 1932. The Mount Sinai Journal of Medicine, New York. 2000;67(3):174-89.
• 2. Jowett S, Seal C, Pearce M, Phillips E, Gregory W, Barton J, et al. Influence of dietary factors on the clinical course of ulcerative colitis: a prospective cohort study. Gut. 2004;53(10):1479-84.
• 3. Higuchi LM, Khalili H, Chan AT, Richter JM, Bousvaros A, Fuchs CS. A prospective study of cigarette smoking and the risk of inflammatory bowel disease in women. The American journal of gastroenterology. 2012;107(9):1399.
• 4. Ananthakrishnan AN, Khalili H, Konijeti GG, Higuchi LM, de Silva P, Fuchs CS, et al. Sleep duration affects risk for ulcerative colitis: a prospective cohort study. Clinical Gastroenterology and Hepatology. 2014;12(11):1879-86.
• 5. Cosnes J, Gower–Rousseau C, Seksik P, Cortot A. Epidemiology and natural history of inflammatory bowel diseases. Gastroenterology. 2011;140(6):1785- 94. e4.
• 6. Ballester Ferré MP, Bosca-Watts MM, Minguez Pérez M. Enfermedad de Crohn. Medicina Clínica. 2018:26-33.
• 7. Peppercorn MA, Kane SV. Clinical manifestations, diagnosis, and prognosis of ulcerative colitis in adults. Up to date [online]. 2011.
• 8. Park SH, Kim D, Ye BD, Yang S-K, Kim J-H, Yang D-H, et al. The Characteristics of Ulcerative Colitis Associated With Autoimmune Pancreatitis. Journal of Clinical Gastroenterology. 2013;47(6):520-5.
• 9. Chaparro M, Ordás I, Cabré E, Garcia-Sanchez V, Bastida G, Peñalva M, et al. Safety of thiopurine therapy in inflammatory bowel disease: long-term followup study of 3931 patients. Inflammatory bowel diseases. 2013;19(7):1404-10.
• 10. Benjamin I, Griggs RC, Fitz JG. Andreoli and Carpenter’s Cecil Essentials of Medicine E-Book: Elsevier Health Sciences; 2015.
• 11. Morris GP, Beck PL, Herridge MS, Depew WT, Szewczuk MR, Wallace JL. Hapten-induced model of chronic inflammation and ulceration in the rat colon. Gastroenterology. 1989;96(2):795-803.
• 12. Cheng J, Shen H, Chowdhury R, Abdi T, Selaru F, Chen JDZ. Potential of Electrical Neuromodulation for Inflammatory Bowel Disease. Inflammatory Bowel Diseases. 2019;26(8):1119-30.
• 13. Briand M-M, Gosseries O, Staumont B, Laureys S, Thibaut A. Transcutaneous Auricular Vagal Nerve Stimulation and Disorders of Consciousness: A Hypothesis for Mechanisms of Action. Frontiers in Neurology. 2020;11(933).
• 14. Hou PW, Hsu HC, Lin YW, Tang NY, Cheng CY, Hsieh CL. The History, Mechanism, and Clinical Application of Auricular Therapy in Traditional Chinese Medicine. Evid Based Complement Alternat Med. 2015;2015:495684.
• 15. Mertens A, Raedt R, Gadeyne S, Carrette E, Boon P, Vonck K. Recent advances in devices for vagus nerve stimulation. Expert review of medical devices. 2018;15(8):527- 39.
• 16. Vagus Nerve Stimulation (VNS) Device For Animal Research. https://vagustim.io/vagus-nerve-stimulation-animal-research-2/ (01.01.2022).
• 17. Duan S, Du X, Chen S, Liang J, Huang S, Hou S, et al. Effect of vitexin on alleviating liver inflammation in a dextran sulfate sodium (DSS)-induced colitis model. Biomedicine & Pharmacotherapy. 2020;121:109683.
• 18. Zhang L, Zhao Y, Fan L, Xu K, Ji F, Xie Z, et al. Tectorigenin protects against experimental fulminant hepatic failure by regulating the TLR4/mitogenactivated protein kinase and TLR4/nuclear factor‐κB pathways and autophagy. Phytotherapy Research. 2019;33(4):1055-64.
• 19. Fusco R, Cordaro M, Siracusa R, D’Amico R, Genovese T, Gugliandolo E, et al. Biochemical evaluation of the antioxidant effects of hydroxytyrosol on pancreatitis-associated gut injury. Antioxidants. 2020;9(9):781.
• 20. Fusco R, Cordaro M, Siracusa R, D’Amico R, Genovese T, Gugliandolo E, et al. Biochemical evaluation of the antioxidant effects of hydroxytyrosol on pancreatitis-associated gut injury. Antioxidants. 2020;9(9):781.
• 21. Kim H-S, Berstad A. Experimental colitis in animal models. Scandinavian journal of gastroenterology. 1992;27(7):529-37.
• 22. Duan S, Du X, Chen S, Liang J, Huang S, Hou S, et al. Effect of vitexin on alleviating liver inflammation in a dextran sulfate sodium (DSS)-induced colitis model. Biomedicine & Pharmacotherapy. 2020;121:109683.
• 23. Lunder AK, Hov JR, Borthne A, Gleditsch J, Johannesen G, Tveit K, et al. Prevalence of Sclerosing Cholangitis Detected by Magnetic Resonance Cholangiography in Patients With Long-term Inflammatory Bowel Disease. Gastroenterology. 2016;151(4):660-9.e4.
• 24. Değer C, Erbil Y, Giriş M, Yanik BT, Tunca F, Olgaç V, et al. The Effect of Glutamine on Pancreatic Damage in TNBS-Induced Colitis. Digestive Diseases and Sciences. 2006;51(10):1841-6.
• 25. Lindgren S, Lilja B, Rosen I, Sundkvist G. Disturbed autonomic nerve function in patients with Crohn’s disease. Scandinavian journal of gastroenterology. 1991;26(4):361- 6.
• 26. Ghia J-E, Blennerhassett P, El-Sharkawy RT, Collins SM. The protective effect of the vagus nerve in a murine model of chronic relapsing colitis. American Journal of Physiology-Gastrointestinal and Liver Physiology. 2007;293(4):G711-G8.
• 27. Meregnani J, Clarençon D, Vivier M, Peinnequin A, Mouret C, Sinniger V, et al. Anti-inflammatory effect of vagus nerve stimulation in a rat model of inflammatory bowel disease. Autonomic Neuroscience. 2011;160(1):82-9.
• 28. Rawat JK, Roy S, Singh M, Guatam S, Yadav RK, Ansari MN, et al. Transcutaneous vagus nerve stimulation regulates the cholinergic antiinflammatory pathway to counteract 1, 2-dimethylhydrazine induced colon carcinogenesis in albino wistar rats. Frontiers in pharmacology. 2019;10:353.