تأثیر تجویز مناکوئینون-4 بر بیان ژن‌های عوامل پیش‌برنده التهاب به دنبال ایسکمی/ ریپرفیوژن مغزی سرتاسری گذرا در هیپوکامپ موش صحرایی نر نژاد ویستار

نوع مقاله : مقاله پژوهشی

نویسندگان

1 دانشجوی دکتری فیزیولوژی جانوری، گروه زیست‌شناسی، دانشکده علوم، دانشگاه فردوسی مشهد، مشهد، ایران

2 استاد، گروه زیست‌شناسی، دانشکده علوم، دانشگاه فردوسی مشهد، مشهد، ایران

چکیده

زمینه و هدف: مطالعات فراوانی نشان داده است که فرایندهای التهابی ناشی از ایسکمی/ ریپرفیوژن مغزی، منجر به ایجاد آسیب­های مغزی و اختلالات شناختی می­گردد. از سوی دیگر، مناکوئینون-4 (MK-4)، یکی از مهم‌ترین انواع ویتامین کا (K2)، دارای تأثیرات ضدالتهابی است؛ لذا در این مطالعه، تأثیرات تجویز MK-4 بر میزان بیان ژن‌های عوامل پیش‌برنده التهاب به دنبال ایسکمی/ ریپرفیوژن مغزی سرتاسری در هیپوکامپ موش­های صحرایی نر بررسی گردید.
مواد و روش‌ها: در این تحقیق، 20 موش صحرایی نر بالغ نژاد ویستار با وزن تقریبی 300 تا 250 گرم به‌طور تصادفی، انتخاب و در ۵ گروه آزمایشی بررسی شدند: گروه کنترل (سالم)، شم (جراحی، بدون بستن شریان­های کاروتید)،‌ ایسکمی/ ریپرفیوژن،‌ ایسکمی/ ریپرفیوژن + تزریق درون‌صفاقی DMSO به‌عنوان حلال MK-4، درمان (ایسکمی/ ریپرفیوژن + تزریق درون‌صفاقی MK-4). به‌منظور ایجاد مدل ایسکمی هر دو شریان کاروتید مشترک به مدت 20 دقیقه مسدود شدند. در گروه درمانی، تجویز درون‌صفاقی MK-4 (mg/kg200) ۲۰ دقیقه پس از ایسکمی (بلافاصله و 2 ساعت پس از ریپرفیوژن) انجام شد. 24 ساعت پس از ریپرفیوژن، میزان mRNA ژن‌های TNF-α، IL-1β و IL-6 بررسی گردید.
یافته‌ها: تجویز درون‌صفاقی MK-4 به‌طور معنی‌داری میزان بیان mRNA ژن­های عوامل پیش‌برنده التهابی شامل TNF-α (p <0.05)، IL-1β و IL-6 (p <0.001) به دنبال ایسکمی/ ریپرفیوژن را کاهش داد.
نتیجه‌گیری: نتایج این تحقیق نشان می‌دهد که تجویز MK-4 پس از القای ایسکمی/ ریپرفیوژن مغزی توانسته است موجب کاهش بیان عوامل پیش‌برنده التهاب در هیپوکامپ شود و احتمالاً از این طریق منجر به بروز اثرات حفاظت نورونی می‌شود.

کلیدواژه‌ها

موضوعات


عنوان مقاله [English]

The effect of Menaquinone-4 administration on the expression of proinflammatory factors following transient global cerebral ischemia/reperfusion in the hippocampus of male Wistar rat

نویسندگان [English]

  • Bahram Farhadi Moghaddam 1
  • Masoud Fereidoni 2
1 PhD Student in Animal Physiology, Dept. of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran
2 Professor, Dept. of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran
چکیده [English]

Introduction: Many investigations revealed that the inflammatory process induced by cerebral ischemia/reperfusion causes brain damages and cognitive impairments. On the other hand, Menaquinone-4 (MK-4) is one of the important vitamin K2 types that has anti-inflammatory effects. Therefore, in this study, we investigated the effect of administration of MK-4 on the level of gene expression of proinflammatory cytokines following global ischemia/reperfusion in the hippocampus of male Wistar rats. Materials and Methods: In this research, 20 adult male Wistar rats (250-300 g) were randomly selected in 5 experimental groups and studied: control (intact), sham (surgery without carotid artery occlusion), ischemia/reperfusion, ischemia/reperfusion + intraperitoneal (i.p.) injection of DMSO as MK-4 solvent, treatment (ischemia/reperfusion + i.p. injection of MK-4). For induction ischemic model, common carotid occlusion was performed for 20 minutes. In the treatment group i.p. injection of 200 mg/kg MK-4 was done 20 minutes after obstruction (immediately and 2 hours after reperfusion). 24 hours after reperfusion, mRNA expression level of TNF-α, IL-1β and IL-6 were assessed. Results: I.p. administration of MK-4 could significantly decrease mRNA expression level of TNF-α (p < 1.15), IL-1β and IL-6 (p < 0.001) induced by ischemia/reperfusion.
Conclusion: The findings of this study show that MK-4 administration following cerebral ischemia/reperfusion could diminish the expression of the pro-inflammatory factors in the hippocampus and maybe cause neuroprotective effects.
Received.

کلیدواژه‌ها [English]

  • Menaquinone-4 (Menatetrenone)
  • Transient cerebral ischemia
  • Tumor Necrosis Factor-alpha
  • Interleukin-1beta
  • Interleukin-6
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