ارزیابی تجربی تاثیر زیپمت بر روی ترمیم زخم ناشی از سوختگی در قرنیه خرگوش

نوع مقاله : مقاله کامل

نویسندگان

1 دانش آموخته دکتری حرفه ای واحد علوم و تحقیقات، دانشگاه آزاد اسلامی، تهران، ایران

2 گروه جراحی دامپزشکی، واحد علوم و تحقیقات، دانشگاه آزاد اسلامی، تهران، ایران

3 گروه پاتوبیولوژی، واحد علوم و تحقیقات، دانشگاه آزاد اسلامی، تهران، ایران

چکیده

هدف از انجام این تحقیق، مطالعه تجربی اثر زیپمت بر روی ترمیم زخم سوختگی قرنیه در خرگوش است. در این مطالعه از 20 سر خرگوش نیوزلندی نر بالغ با دامنه وزنی 2.5_3 کیلوگرم سالم استفاده گردید. بعد از بیهوشی عمومی، زخم قرنیه در چشم چپ تمام حیوانات ایجاد شد.چشم چپ هر کدام از خرگوش‌ها با 2 قطره تتراکایین 5/0% آغشته شد و پس از 5 دقیقه کاغذ صافی مدور به قطر 6 میلی‌متر که آغشته به 30 میکرولیتر سود یک نرمال است، برای مدت 60 ثانیه در مرکز قرنیه قرار داده ‌شد. بعد از برگشت از بی هوشی، خرگوش‌ها به 4 گروه 5 تایی تقسیم شدند. سپس در گروه اول، دوم و سوم به ترتیب  با زیپمت  50 ،100 و mg/kg 200 گاواژ انجام شد و در گروه چهارم آب مقطر تا 21 روز بعد از ایجاد زخم قرنیه روزانه گاواژ شد. بعد از 21 روز ایجاد سوختگی قرنیه، نمونه‌های بافتی از محل زخم اخذ و تحت بررسی آسیب شناسی بافتی قرار گرفتند.با توجه به مطالعات آسیب شناختی شاخص‌های عروق‌زایی، میزان التهاب و ادم بستره قرنیه در خرگوش‌های تحت درمان با زیپمت mg/kg 200 در مقایسه با گروه شاهد بطور معنی‌داری کاهش اما لایه‌های بافت پوششی قرنیه افزایش یافته بود (05/0>p). همچنین استفاده از زیپمت موجب بهبود نظم طبیعی رشته‌های کلاژن قرنیه شد (05/0>p). بر اساس نتایج به دست آمده به نظر می‌رسد که زیپمت با دوز پیشنهادی mg/kg 200 اثرات مناسب و قابل قبولی بر روند التیام بخشی و ترمیم زخم قرنیه خرگوش داشته باشد.

کلیدواژه‌ها


عنوان مقاله [English]

Experimental study of the effect of Zipmet on corneal ulcer healing due to burning in rabbit

نویسندگان [English]

  • Alireza Mahlojiyan 1
  • Alireza Jahandideh 2
  • Ahmad Asghari 2
  • Pezhman Mortezavi 3
1 Graduated from DVM Professional Science and Research Unit, Islamic Azad University, Tehran, Iran.
2 Department of Veterinary Surgery, Science and Research Unit, Islamic Azad University, Tehran, Iran
3 Department of Pathobiology, Science and Research Unit, Islamic Azad University, Tehran, Iran
چکیده [English]

This study was conducted to examine the effect of Zipmet on healing of corneal ulcer due to burning in rabbit. In this study, 20 adult healthy male NewZealand rabbits with an average weight of 2.5-3 kg were used. After general anesthesia, corneal ulcer in the left eye of the all animals was induced.The left eye of each rabbit was stained with 2 drops of tetraquine 0.05% . After 5 minutes, a circular filter paper of 6 mm in diameter, impregnated with 30 μL of a Sodium hydroxide 1 was placed in the cornea center for 60 seconds.After returning from anesthesia, the rabbits were randomly divided into 4 groups of 5 numbers. Then, in the first, second and third groups, Zipmet at 50, 100 and 200 mg / kg were gavaged, while the fourth group was gavaged with water for 21 days. After 21 days, corneal samples were taken and evaluated histopathologically. According to the histopathological findings, vascularization, inflammation and matrix edema of cornea significantly marked while the epithelium of cornea increased in metformin 200 mg / kg -treated rabbits compared to control group (P<0.05). Also, administration of Zipmet significantly improved the natural structure of cornea collagen fibers (P<0.05). Based on the results, it seems that Zipmet at dose of 200 mg / kg has useful effect on the healing process in rabbit’s corneal ulcer.

کلیدواژه‌ها [English]

  • Corneal ulcer
  • Zipmet
  • NaOH
  • New Zealand Rabbit
1. Cejkova, J., Vejrazka, M., Plateník, J. and Stípek, S. 2004. Agerelated changes in superoxide dismutase, glutathione peroxidase, catalase and xanthine oxidoreductase /xanthine oxidase activities in the rabbit cornea. Experimental gerontology, 39(10): 1537-1543.
2. Cooper, D., Chitman, K.D., Williams, M.C. and Granger, D.N. 2003. Time-dependent platelet-vessel wall interactions induced by intestinal ischemia-reperfusion. American Journal of Physiology, 284: G1027–G1033.
3. Cheng, J., Truong, L. D., Wu, X., Kuhl, D., Lang, F. and Du, J. 2010. Serum-and glucocorticoid-regulated kinase 1 is upregulatedfollowing unilateral ureteral obstruction causing epithelial–mesenchymal transition. Kidney international, 78(7): 668-678.
4. Detaille, D., Guigas, B., Chauvin, C., Batandier, C., Fontaine, E., Wiernsperger, N. and Leverve, X. 2005. Metformin prevents high-glucose–induced endothelial cell death through a mitochon mitochondrial permeability transition-dependent process. Diabetes, 54(7): 2179-2187.
5. Gadsby, R., 2009. Efficacy and safety of sitagliptin in the treatment of type 2 Diabetes. Clinical Medicine Therapeutics (1): 53-62.
6. Gawaz, M., Langer, H. and May, A.E. 2005. Platelets in inflammation and atherogenesis. Journal of Clinical Investigation ., 11(5): 3378-3384.
7. Goshman L. 1999 . Diabetes; New oral medications, new attitudes. journal pharmacy society of wisconsin.,16(2): 22-30.
8. Herman, G. A., Stevens, C., van Dyck, K., Bergman, A., Yi, B., De Smet, M., Snyder, K., Hilliard, D., Tanen, M., Tanaka, W., Wang, A.Q., Zeng, W., Musson, D., Winchell, G., Davies, M. J., Ramael, S., Gottesdiener, K. M., Wagner, J. A. 2005. Pharmacokinetics and pharmacodynamics of sitagliptin, an inhibitor of dipeptidyl peptidase IV, in healthy subjects results from two randomized, double-blind, placebo-controlled studies with single oral doses. Clinical Pharmacology & Therapeutics., 78(6): 675-88.
9. Hou, X., Song, J., Li, X.-N., Zhang, L., Wang, X., Chen, L. and Shen, Y. H. 2010. Metformin reduces intracellular reactive oxygen species levels by upregulating expression of the antioxidant thioredoxin via the AMPK-FOXO3 pathway. Biochemical and biophysiSteuhl, K. P. 2000. Amniotic membrane transplantation for acute chemical or thermal burns. Ophthalmology, 107(5): 980-989.
10. Isoda, K., Young, J. L., Zirlik, A., MacFarlane, L. A., Tsuboi, N., Gerdes, N., Schönbeck, U. and Libby, P. 2006. Metformin inhibits proinflammatory responses and nuclear factor-κB in humanvascular wall cells. Arteriosclerosis, thrombosis, and vascular biology, 26(3): 611-617.
11. Jian M-Y, Alexeyev MF, Wolkowicz PE, Zmijewski JW, Creighton JR. 2013. Metformin-stimulated AMPK-α1 promotes microvascular repair in acute lung injury. American Journal of Physiology-Lung Cellular and Molecular Physiology. 305(11):L844-L55.
12. Josephkutty S,Potter JM.Comparsion of tolbutamid and metformin in elderly diabetic patients.Duabetic Med 1990;7: 5104.
13. Kato S, Oshika T, Numaga J, Kawashima H, Kitano S, Kaiya T. 2000 . Influence of rapid glycemic control on lens opacity in patients with diabetes mellitus. Am J Ophthalmol,130:354-355
14. Khaksar, E., Aldavood, S., Abedi, G., Sedaghat, R., Nekoui, O. and Zamani-ahmadmahmudi, M. 2013. The effect of sub-conjunc tival platelet-rich plasma in combination with topical acetylcysteine on corneal alkali burn ulcer in rabbits. Comparative Clinical Pathology, 22)1(:107-112.
15. Kuligowski, M.P., Kitching, A.R. and Hickey M.J. 2006. Leukocyte recruitment to the inflamed glomerulus: a critical role for platelet-derived P-selectin in the absence of rolling. Journal of Immunology, 176: 6991–6999.
16. Nishijima, K., Kiryu, J. and Tsujikawa, A., et al. 2004. Platelets adhering to the vascular wall mediate postischemic leukocyte-endothelial cell interactions in retinal microcirculation. Invest. Ophthalmol. Vis. Sci., 45: 977–984.
17. Park CS, Bang B-R, Kwon H-S, Moon K-A, Kim T-B, Lee K-Y, et al. 2012. Metformin reduces airway inflammation and remodeling via activation of AMP-activated protein kinase. Biochemical pharmacology. 84:1660-70.
18. Pierce, G.F., Mustoe, T.A., Altrock, B.W., Deuel, T.F. and Thomason, A. 1991. Role of platelet-derived growth factor in wound healing. Journal of Cell Biochemistry, 45: 319-326.
19. Product information:Glucophage ®, Glucophage ®, ,XR.Bristol- Myers.Squibb.Princeton,NJ.08543 USA revised 1/2001) reviewed june 2001,available in site:http//www.chfpatients.com.
20. R.M. and Borke, J.L. 2014. Effect of metformin on periimplant wound healing in a rat model of type 2 diabetes. Implant Dentistry, 223(3):319-27.
21. Reid B., Song, B., Colin, D. and Zhao, M. 2000. Wound healing in rat cornea: the role of electric currents Ophthalmology Journal, 107: 1347-1351.
22. Shoham, A., Hadziahmetovic, M., Dunaief, J. L., Mydlarski, M. B. and Schipper, H. M. 2008. Oxidative stress in diseases of the human cornea. Free Radical Biology and Medicine, 45(8): 1047-1055.
23. Strubbe DT, Brooks DE, Schultz GS, Willis‐Goulet H, Gelatt KN, Andrew SE, et al. 2000. Evaluation of tear film proteinases in horses with ulcerative keratitis. Veterinary Ophthalmology. 3(2‐3):111-9.
24. Wilson, S.E., Mohan, R.R., Ambrosio, Jr. R., Hong, J., Lee, J. 2001.The Corneal Wound Healing Response Cytokine-mediated Interaction of the Epithelium Stroma and Inflammatory Cells. Progress in retinal and eye research, 20(5):625-37.
25. Zhijie, L., Rolando, E., Rumbaut Alan, R.B., and Wayne Smith, C. 2003. Platelet response to corneal abrasion is necessary for acute inflammation and efficient re-epithelialization, FASEB Journal, 17: 397–407.