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Salimi, Rahil, Shirpoor, Alireza, Naderi, Roya. (1404). miR‑429 and GATA4 may participate in cerebral ischemic stroke by regulating autophagy and apoptosis: the effect of Chlorogenic acid. سامانه مدیریت نشریات علمی, 80(4), 945-955. doi: 10.32592/ARI.2025.80.4.945
Rahil Salimi; Alireza Shirpoor; Roya Naderi. "miR‑429 and GATA4 may participate in cerebral ischemic stroke by regulating autophagy and apoptosis: the effect of Chlorogenic acid". سامانه مدیریت نشریات علمی, 80, 4, 1404, 945-955. doi: 10.32592/ARI.2025.80.4.945
Salimi, Rahil, Shirpoor, Alireza, Naderi, Roya. (1404). 'miR‑429 and GATA4 may participate in cerebral ischemic stroke by regulating autophagy and apoptosis: the effect of Chlorogenic acid', سامانه مدیریت نشریات علمی, 80(4), pp. 945-955. doi: 10.32592/ARI.2025.80.4.945
Salimi, Rahil, Shirpoor, Alireza, Naderi, Roya. miR‑429 and GATA4 may participate in cerebral ischemic stroke by regulating autophagy and apoptosis: the effect of Chlorogenic acid. سامانه مدیریت نشریات علمی, 1404; 80(4): 945-955. doi: 10.32592/ARI.2025.80.4.945

miR‑429 and GATA4 may participate in cerebral ischemic stroke by regulating autophagy and apoptosis: the effect of Chlorogenic acid

Archives of Razi Institute
مقاله 16، دوره 80، شماره 4، مهر و آبان 2025، صفحه 945-955    اصل مقاله (645.11 K)
نوع مقاله: Original Articles
شناسه دیجیتال (DOI): 10.32592/ARI.2025.80.4.945
نویسندگان
Rahil Salimi1؛ Alireza Shirpoor2؛ Roya Naderi* 2، 3
1Student Research Committee, Urmia University of Medical Sciences, Urmia, Iran.
2Department of Physiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran.
3Neurophysiology Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran.
چکیده
Abstract
Autophagy is a double-edged sword for maintaining neural system homeostasis during development of cerebral ischemia. However, the potential molecular mechanisms behind that remain unclear. This study investigated the miR-429 and its target GATA4 alterations, autophagy mediators and apoptosis in ischemic stroke alone and also in combination with chlorogenic acid (CGA).
Male Wistar rats were assigned into three groups (n=8): sham, IR (ischemia-reperfusion, ischemia-reperfusion, transient cerebral ischemia inducing by common carotid artery occlusion and reperfusion), IR+CGA (30 mg/kg, ip; intraperitoneally, 10 minutes prior to ischemia and 10 minutes before reperfusion.). miR-429, GATA4, c-Caspase-3/p-Caspase-3 ratio, LC3-I, LC3-II, Beclin1 and p62 measured by Real time PCR and also Western blot assays. At the end of the experiment, we observed increased miR-429 gene expression (P<0.05) and c-Caspase-3/p-Caspase-3 ratio (P<0.01) as well as decreased GATA4 protein expression (P<0.001) in IR group. In addition, autophagy was over-activated markedly in the brain of CCAO rats as evidenced by an increased ratio of LC3-II/I and Beclin1 protein expression and decreased expression of p62 after 24 h of reperfusion (P<0.001). Moreover, immunohistochemistry studies found that cerebral IR significantly increased the ratio of total LC3 immunoreactivity in the cortex tissue of male rats (P<0.001). Treatment with CGA significantly attenuated autophagic activity as well as apoptosis and reversed aforementioned molecule levels. Taken together, these results suggested that ischemic insult can increase autophagic activities and apoptosis possibly by miR‑429 and GATA4 alterations in the brain cortex after cerebral IR insult which can be alleviated by CGA as a potential therapy for someone afflicted with ischemia.
کلیدواژه‌ها
ischemia-reperfusion؛ brain؛ chlorogenic acid
عنوان مقاله [English]
نقش miR‑429 و GATA4 در سکته مغزی ایسکمیک از طریق اتوفاژی و آپوپتوز: اثر اسید کلروژنیک
چکیده [English]
اتوفاژی یک شمشیر دولبه برای حفظ هموستاز سیستم عصبی در طول ایجاد ایسکمی مغزی است. با این حال، مکانیسم‌های مولکولی بالقوه پشت آن نامشخص است. این مطالعه به بررسی miR-429 و تغییرات GATA4 و همچنین واسطه‌های اتوفاژی و آپوپتوز در سکته مغزی ایسکمیک به تنهایی و در ترکیب با اسید کلروژنیک (CGA) پرداخت. موش های صحرایی نر نژاد ویستار به سه گروه تقسیم شدند (در هر گروه 8 موش): گروه شم، ایسکمی-ریپرفیوژن ( با بستن هر دو شریان کاروتید مشترک)، ایسکمی-ریپرفیوژن+CGA (با دوز 30 میلی گرم بر کیلوگرم بصورت داخل صفاقی ده دقیقه قبل از ایسکمی و ده دقیقه قبل از خونرسانی مجدد). miR-429، GATA4، c-Caspase-3/p-Caspase-3، LC3-I، LC3-II، Beclin1 و p62 توسط Real Time PCR و Western blot اندازه گیری شد. افزایش بیان ژن (P<0.05)miR-429 و c-Caspase-3/p-Caspase-3 (P<0.01) و همچنین کاهش بیان پروتئین GATA4 (P<0.001) در گروه IR مشاهده شد. علاوه بر این، اتوفاژی در مغز CCAO افزایش داشت که با افزایش نسبت LC3-II/I و بیان پروتئین Beclin1 و کاهش بیان p62 پس از 24 ساعت خون‌رسانی مجدد نشان داد (P<0.001) . علاوه بر این، مطالعات ایمونوهیستوشیمی نشان داد که IR مغزی به طور قابل‌توجهی مقدار کل LC3 را در بافت قشر موش‌های نر افزایش داد (P<0.001) . درمان با CGA به طور قابل توجهی فعالیت اتوفاژیک و همچنین آپوپتوز را کاهش داد و سطوح مولکولی فوق را معکوس کرد. در مجموع، این نتایج نشان داد که ایسکمی می‌تواند فعالیت‌های اتوفاژیک و آپوپتوز را احتمالاً با تغییرات miR-429 و GATA4 در قشر مغز پس از آسیب IR مغزی افزایش دهد که توسط CGA به عنوان یک درمان بالقوه برای افرادی که به ایسکمی مبتلا هستند کاهش یابد.
کلیدواژه‌ها [English]
ایسکمی-ریپرفیوژن, مغز, اسید کلروژنیک
سایر فایل های مرتبط با مقاله
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