جلد 26، شماره 2 - ( 2-1398 )                   جلد 26 شماره 2 صفحات 84-74 | برگشت به فهرست نسخه ها

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دانشگاه آزاد اسلامی، واحد تهران شمال، تهران، ایران ، m.movahhedi@iau-tnb.ac.ir
چکیده:   (3527 مشاهده)
زمینه و هدف: واحد p65، یکی از زیر واحدهای NF-κB می‌باشد و فسفوریلاسیون آن توسط استرس اکسیداتیو باعث فعال شدن NF-κB می‌گردد. هدف از پژوهش حاضر، بررسی اثر تزریق آدنوزین پس از ایسکمی ریپرفیوژن مغزی بر بیان ژن NF-κB /p65 و سطح فعالیت گونه‌های واکنشگر اکسیژن (Reactive Oxygen Species-ROS) بافت هیپوکامپ مغز در موش‌های نر ویستار است.
روش کار: 40 سر موش نر نژاد ویستار به‌طور تصادفی به 4 گروه کنترل سالم (10=n)، گروه ایسکمی ریپرفیوژن (10=n)، گروه ایسکمی ریپرفیوژن + آدنوزین دوز 1/0 میلی‌گرم بر کیلوگرم (10=n) و گروه ایسکمی ریپرفیوژن + آدنوزین دوز 4/0 میلی‌گرم بر کیلوگرم (10=n) تقسیم شدند. ایسکمی در حیوانات توسط بستن شریان کاروتید به مدت 45 دقیقه ایجاد شد. تزریق داخل صفاقی آدنوزین 24 ساعت بعد از ایسکمی انجام شد. بیان ژن NF-κB /p65 و فعالیت ROS، به ترتیب توسط Real time PCR و اسپکتروفلوریمتر اندازه گیری شدند. از تحلیل واریانس یک طرفه و آزمون تعقیبی بونفرونی جهت تحلیل داده‌ها استفاده گردید. سطح معنی‌داری 05/0>p بود.
یافته‌ها: نتایج نشان داد، ایسکمی موجب افزایش معنی‌دار بیان ژن NF-κB /p65 و فعالیت ROS در مقایسه با گروه کنترل شد (05/0>p). همچنین هر دو دوز آدنوزین نیز منجر به کاهش معنی‌دار بیان ژن NF-κB /p65 و فعالیت ROS در مقایسه با گروه ایسکمی شد (05/0>p).
نتیجه‌گیری: ایسکمی ریپرفیوژن مغزی باعث استرس اکسیداتیو می‌شود. به نظر می‌رسد، تزریق آدنوزین در کاهش استرس اکسیداتیو و التهاب ناشی از ایسکمی ریپرفیوژن مغزی مؤثر باشد.
 
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نوع مطالعه: پژوهشي | موضوع مقاله: بیوشیمی

فهرست منابع
1. 1. Zhou J, Li M, Jin WF, Li XH, Zhang YY. Role of NF-κB on Neurons after Cerebral Ischemia Reperfusion. Int J Pharmacol; 2018.14(4):451-9.
2. 2. He Y, Wan H, Du Y, Bie X, Zhao T, Fu W, et al. Protective effect of Danhong injection on cerebral ischemia–reperfusion injury in rats. J Ethnopharmacol; 2012.144(2):387-94.
3. 3. Bin J, Wang Q, Zhuo YY, Xu JP, Zhang HT. Piperphentonamine (PPTA) attenuated cerebral ischemia-induced memory deficits via neuroprotection associated with anti-apoptotic activity. Metabol Brain Dis; 2012.27(4):495-505.
4. 4. Payabvash S, Souza LC, Wang Y, Schaefer PW, Furie KL, Halpern EF, et al. Regional ischemic vulnerability of the brain to hypoperfusion: the need for location specific computed tomography perfusion thresholds in acute stroke patients. Stroke; 2011:STROKEAHA. 110.600940.
5. 5. Farhangi D, Sharifi ZN, Movassghi S. Evaluation of neuroprotective effect of propofol on pyramidal neurons in CA1 region of hippocampus among male lab rats following ischemia/transient overall reperfusion. Med Sci J Islam Azad Uni; 2016.26(3):149-56.
6. 6. Kovalenko T, Osadchenko I, Nikonenko A, Lushnikova I, Voronin K, Nikonenko I, et al. Ischemia‐induced modifications in hippocampal CA1 stratum radiatum excitatory synapses. Hippocampus; 2006.16(10):814-25.
7. 7. Granger DN, Kvietys PR. Reperfusion injury and reactive oxygen species: the evolution of a concept. Redox Biol; 2015.6:524-51.
8. 8. Liu H, Zhang X, Du Y, Ji H, Li S, Li L, et al. Leonurine protects brain injury by increased activities of UCP4, SOD, CAT and Bcl-2, decreased levels of MDA and Bax, and ameliorated ultrastructure of mitochondria in experimental stroke. Brain Res; 2012.1474:73-81.
9. 9. Crack PJ, Wong CH. Modulation of neuro-inflammation and vascular response by oxidative stress following cerebral ischemia-reperfusion injury. Curr Med Chem; 2008.15(1):1-14.
10. 10. Chen SD, Yang DI, Lin TK, Shaw FZ, Liou CW, Chuang YC. Roles of oxidative stress, apoptosis, PGC-1α and mitochondrial biogenesis in cerebral ischemia. Int J Mol Sci; 2011.12(10):7199-215.
11. 11. Zarringol M. A review on regulation of autophagy by ROS (Reactive Oxygen Species). Razi J Med Sci; 2018.24(11):93-105.
12. 12. Grenz A, Homann D, Eltzschig HK. Extracellular adenosine: a safety signal that dampens hypoxia-induced inflammation during ischemia. Antioxid Redox Signal; 2011.15(8):2221-34.
13. 13. Fredholm BB, IJzerman AP, Jacobson KA, Klotz KN, Linden J. International ::::union:::: of Pharmacology. XXV. Nomenclature and classification of adenosine receptors. Pharmacol Rev; 2001.53(4):527-52.
14. 14. Laubach VE, French BA, Okusa MD. Targeting of adenosine receptors in ischemia–reperfusion injury. Expert Opinion Ther Targets; 2011;15(1):103-18.
15. 15. Rudolphi KA, Schubert P, Parkinson FE, Fredholm BB. Neuroprotective role of adenosine in cerebral ischaemia. Trends Pharmacol Sci; 1992.13:439-45.
16. 16. Pearson T, Damian K, Lynas RE, Frenguelli BG. Sustained elevation of extracellular adenosine and activation of A1 receptors underlie the post‐ischaemic inhibition of neuronal function in rat hippocampus in vitro. J Neurochem; 2006.97(5):1357-68.
17. 17. Park SW, Kim JY, Ham A, Brown KM, Kim M, D'Agati VD, et al. A1 adenosine receptor allosteric enhancer PD-81723 protects against renal ischemia-reperfusion injury. Am J Physiol-Renal Physiol; 2012.303(5):F721-F32.
18. 18. Jhaveri KA, Toth LA, Sekino Y, Ramkumar V. Nitric oxide serves as an endogenous regulator of neuronal adenosine A1 receptor expression. J Neurochem; 2006.99(1):42-53.
19. 19. Wang YH, Wang WY, Chang CC, Liou KT, Sung YJ, Liao JF, et al. Taxifolin ameliorates cerebral ischemia-reperfusion injury in rats through its anti-oxidative effect and modulation of NF-kappa B activation. J Biomed Sci; 2006.13(1):127-41.
20. 20. Malinin NL, Boldin MP, Kovalenko AV, Wallach D. MAP3K-related kinase involved in NF-kB induction by TNF, CD95 and IL-1. Nature; 1997.385(6616):540.
21. 21. Shen WH, Zhang CY, Zhang GY. Modulation of IkappaB kinase autophosphorylation and activity following brain ischemia. Acta Pharmacol Sin; 2003.24(4):311-5.
22. 22. Peng Y, Gallagher SF, Landmann R, Haines K, Murr MM. The role of p65 NF-kB/RelA in pancreatitis-induced kupffer cell apoptosis. J Gastrointes Surg; 2006.10(6):837-47.
23. 23. Bohuslav J, Chen LF, Kwon H, Mu Y, Greene WC. p53 induces NF-κB activation by an IκB kinase-independent mechanism involving phosphorylation of p65 by ribosomal S6 kinase 1. J Biol Chem; 2004.279(25):26115-25.
24. 24. Takada Y, Mukhopadhyay A, Kundu GC, Mahabeleshwar GH, Singh S, Aggarwal BB. Hydrogen peroxide activates NF-κB through tyrosine phosphorylation of IκBα and serine phosphorylation of p65 evidence for the involvement of IκBα kinase and Syk protein-tyrosine kinase. J Biol Chem; 2003.278(26):24233-41.
25. 25. Qian Y, Guan T, Huang M, Cao L, Li Y, Cheng H, et al. Neuroprotection by the soy isoflavone, genistein, via inhibition of mitochondria-dependent apoptosis pathways and reactive oxygen induced-NF-κB activation in a cerebral ischemia mouse model. Neurochem Int; 2012.60(8):759-67.
26. 26. Crack PJ, Taylor JM, Ali U, Mansell A, Hertzog PJ. Potential contribution of NF-κB in neuronal cell death in the glutathione peroxidase-1 knockout mouse in response to ischemia-reperfusion injury. Stroke; 2006.37(6):1533-8.
27. 27. Phillips JB, Williams AJ, Adams J, Elliott PJ, Tortella FC. Proteasome inhibitor PS519 reduces infarction and attenuates leukocyte infiltration in a rat model of focal cerebral ischemia. Stroke; 2000.31(7):1686-93.
28. 28. Crack PJ, Taylor JM. Reactive oxygen species and the modulation of stroke. Free Rad Biol Med; 2005.38(11):1433-44.
29. 29. Chen X, Kandasamy K, Srivastava RK. Differential roles of RelA (p65) and c-Rel subunits of nuclear factor κB in tumor necrosis factor-related apoptosis-inducing ligand signaling. Cancer Res; 2003.63(5):1059-66.
30. 30. Zhu T, Yao Q, Wang W, Yao H, Chao J. iNOS induces vascular endothelial cell migration and apoptosis via autophagy in ischemia/reperfusion injury. Cell Physiol Biochem; 2016.38(4):1575-88.
31. 31. Mirghani SJ PM, Yaghoobpour Yekani O, Zamani M, Feizolahi F, Nikbin S, Derakhshideh A, et al. Role or synergistic interaction of adenosine and vitamin D3 versus high intensity interval training and isocaloric moderate intensity training: An experimental protocol. JMIR Res Protocols; 2018:1-21.
32. 32. Chen J, Yang C, Xu X, Yang Y, Xu B. The effect of focal cerebral ischemia-reperfusion injury on TLR4 and NF-κB signaling pathway. Experim Ther Med; 2018.15(1):897-903.
33. 33. Liang J, Luan Y, Lu B, Zhang H, Luo YN, Ge P. Protection of ischemic postconditioning against neuronal apoptosis induced by transient focal ischemia is associated with attenuation of NF-κB/p65 activation. PLoS One; 2014.9(5):e96734.
34. 34. Chen X, Song M, Zhang B, Zhang Y. Reactive oxygen species regulate T cell immune response in the tumor microenvironment. Oxid Med Cell Long; 2016.2016.
35. 35. Beckhauser TF, Francis-Oliveira J, De Pasquale R. Reactive oxygen species: physiological and physiopathological effects on synaptic plasticity: supplementary issue: brain plasticity and repair. J experimneurosci; 2016.10:JEN. S39887.
36. 36. Shen WH, Zhang CY, Zhang GY. Antioxidants attenuate reperfusion injury after global brain ischemia through inhibiting nuclear factor-kappa B activity in rats. Acta Pharmacol Sin; 2003.24(11):1125-30.
37. 37. Terai K, Matsuo A, McGeer EG, McGeer PL. Enhancement of immunoreactivity for NF-κB in human cerebral infarctions. Brain Res; 1996.739(1-2):343-9.
38. 38. Qin WY, Luo Y, Chen L, Tao T, Li Y, Cai YL, et al. Electroacupuncture Could Regulate the NF-B Signaling Pathway to Ameliorate the Inflammatory Injury in Focal Cerebral Ischemia/Reperfusion Model Rats. Evid-Based Complem Alter Med; 2013.2013.
39. 39. Sun BZ, Chen L, Wu Q, Wang HL, Wei XB, Xiang YX, et al. Suppression of inflammatory response by flurbiprofen following focal cerebral ischemia involves the NF-κB signaling pathway. Int J Clin Experim Med; 2014.7(9):3087.
40. 40. Schneider A, Martin-Villalba A, Weih F, Vogel J, Wirth T, Schwaninger M. NF-κB is activated and promotes cell death in focal cerebral ischemia. Nature Med; 1999.5(5):554.
41. 41. Kratsovnik E, Bromberg Y, Sperling O, Zoref-Shani E. Oxidative stress activates transcription factor NF-κB-mediated protective signaling in primary rat neuronal cultures. J Mol Neurosci; 2005.26(1):27-32.
42. 42. Fredholm B. Adenosine, an endogenous distress signal, modulates tissue damage and repair. Cell Death Differ; 2007.14(7):1315.
43. 43. Cunha RA. Neuroprotection by adenosine in the brain: from A 1 receptor activation to A 2A receptor blockade. Purinerg Signal; 2005.1(2):111-34.
44. 44. Saransaari P, Oja SS. Mechanisms of adenosine release in the developing and adult mouse hippocampus. Neurochem Res; 2002.27(9):911-8.
45. 45. Hu S, Dong H, Zhang H, Wang S, Hou L, Chen S, et al. Noninvasive limb remote ischemic preconditioning contributes neuroprotective effects via activation of adenosine A1 receptor and redox status after transient focal cerebral ischemia in rats. Brain Res; 2012.1459:81-90.
46. 46. Takeshima E, Tomimori K, Kawakami H, Ishikawa C, Sawada S, Tomita M, et al. NF-κB activation by Helicobacter pylori requires Akt-mediated phosphorylation of p65. BMC Microbiol; 2009.9(1):36.
47. 47. Beg AA, Finco TS, Nantermet PV, Baldwin AS. Tumor necrosis factor and interleukin-1 lead to phosphorylation and loss of I kappa B alpha: a mechanism for NF-kappa B activation. Mol Cell Biol; 1993.13(6):3301-10.

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