fa اثر حفاظت کننده عصبی گالیک‌اسید بر آسیب حافظه و میزان فاکتور نوروترفیک مشتق از مغز درکورتکس انتورینال مغز نوزادان موش‌های صحرایی متعاقب نارسایی رحمی-جفتی فیزیولوژی Physiology پژوهشي Original article <strong><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">مقدمه: </span></span></strong><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">نارسایی رحمی-جفتی </span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">(</span></span><span dir="LTR"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">Uteroplacental Insufficiency; UPI</span></span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">) </span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">سبب اختلالات تکاملی عصبی در نوزادان دچار محدودیت رشد درون رحمی (</span></span><span dir="LTR"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">Intra Uterine Growth Restriction; IUGR</span></span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">) می&shy;شود. </span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">هدف از این پژوهش، بررسی اثر گالیک‌اسید (</span></span><span dir="LTR"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">Gallic Acid; GA</span></span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">) بر </span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">آسیب </span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">حافظه و سطح فاکتور نوروتروفیک مشتق از مغز (</span></span><span dir="LTR"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">Brain Derived Neurotrophic Factor; BDNF</span></span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">) در قشر انتورینال مغز موش‌های صحرایی مدل </span></span><span dir="LTR"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">UPI</span></span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;"> می&shy;باشد.</span></span><br> <strong><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">روش بررسی:</span></span></strong> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">در این تحقیق تجربی، 40 سر موش صحرایی باردار‌نژاد ویستار در 5 گروه شامل‌کنترل، </span></span><span dir="LTR"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">UPI</span></span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">، </span></span><span dir="LTR"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">UPI+GA100</span></span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">، </span></span><span dir="LTR"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">UPI+GA200</span></span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;"> و </span></span><span dir="LTR"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">UPI+GA400</span></span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;"> به‌صورت تصادفی قرار گرفتند. </span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">در روز 18 بارداری جراحی انسداد کامل شریان‌های رحمی قدامی جهت القاء </span></span><span dir="LTR"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">UPI</span></span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;"> انجام شد. از روز 15 بارداری تا زمان تولد نوزادان، گالیگ‌اسید با دوزهای </span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">1</span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">00، 200 و 400 میلی&shy;گرم بر کیلو&shy;گرم وزن بدن گاواژ شد. ارزیابی حافظه فضایی و کاری در یک ماهگی به‌ترتیب با ماز آبی موریس و </span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">ماز </span></span>&nbsp;<span dir="LTR"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">Y</span></span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">انجام شد. سپس، محتوای </span></span><span dir="LTR"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">BDNF</span></span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;"> در </span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">قشر انتورینال مغز</span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;"> به‌روش الایزا سنجیده شد.</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">داده&shy;ها </span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">با</span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;"> آزمون </span></span><span dir="LTR"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">ANOVA</span></span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;"> و تست تعقیبی توکی توسط نرم&shy;افزار </span></span><span dir="LTR"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">SPSS Inc., Chicago, IL; Version </span></span></span><span dir="LTR"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">16</span></span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;"> تجزیه و تحلیل شدند.</span></span><br> <strong><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">نتایج:</span></span></strong><span style="font-family:b nazanin;"><span style="font-size:12.0pt;"> کاهش معنی&shy;دار حافظه فضایی</span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;"> و کاری</span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;"> و نیز محتوای </span></span><span dir="LTR"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">BDNF</span></span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;"> در قشرانتورینال </span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">گروه </span></span><span dir="LTR"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">UPI</span></span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;"> نسبت به گروه </span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">کنترل </span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">مشاهده گردید (05/0</span></span><span style="font-family:times new roman,serif;"><span style="font-size:12.0pt;">˂</span></span><em><span dir="LTR"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">p</span></span></span></em><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">)</span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">. از طرفی، گروه&shy;های تحت تیمار با </span></span><span dir="LTR"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">GA</span></span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;"> نسبت به گروه </span></span><span dir="LTR"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">UPI</span></span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">، افزایش معنی&shy;داری در سطح </span></span>&nbsp;<span dir="LTR"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">BDNF</span></span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">و بهبود حافظه فضایی و کاری را نشان دادند (05/0</span></span><span style="font-family:times new roman,serif;"><span style="font-size:12.0pt;">˂</span></span><em><span dir="LTR"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">p</span></span></span></em><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">).</span></span><br> <strong><span style="letter-spacing:-.1pt;"><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">نتیجه‌گیری:</span></span></span></strong><span style="letter-spacing:-.1pt;"><span style="font-family:b nazanin;"><span style="font-size:12.0pt;"> محدود‌سازی رشد </span></span></span><span style="letter-spacing:-.1pt;"><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">جنینی ‌متعاقب</span></span></span> <span dir="LTR" style="letter-spacing:-.1pt;"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">UPI </span></span></span><span style="letter-spacing:-.1pt;"><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">با کاهش سطح</span></span></span><span dir="LTR" style="letter-spacing:-.1pt;"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">BDNF</span></span></span><span style="letter-spacing:-.1pt;"><span style="font-family:b nazanin;"><span style="font-size:12.0pt;"> در قشر انتورینال </span></span></span><span style="letter-spacing:-.1pt;"><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">سبب نقص حافظه در موش‌های صحرایی </span></span></span><span style="letter-spacing:-.1pt;"><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">مدل </span></span></span><span style="letter-spacing:-.1pt;"><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">گردید. با این حال، اثرات حفاظت عصبی </span></span></span><span dir="LTR" style="letter-spacing:-.1pt;"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">GA</span></span></span> <span style="letter-spacing:-.1pt;"><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">منجر به افزایش سطح</span></span></span> <span dir="LTR" style="letter-spacing:-.1pt;"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">BDNF </span></span></span><span style="letter-spacing:-.1pt;"><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">و </span></span></span><span style="letter-spacing:-.1pt;"><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">بهبود آسیب شناختی در مدل </span></span></span><span dir="LTR" style="letter-spacing:-.1pt;"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">UPI</span></span></span><span style="letter-spacing:-.1pt;"><span style="font-family:b nazanin;"><span style="font-size:12.0pt;"> می‌گردد.</span></span></span><br> &nbsp; <strong>Introduction:</strong> Uteroplacental insufficiency (UPI) causes neurodevelopmental deficits affecting the intrauterine growth restricted (IUGR) offspring. This study aimed to analyze the effects of Gallic acid (GA) on memory deficit and brain-derived neurotrophic factor (BDNF) content in entorhinal cortex of UPI rat models.<br> <strong>Methods:</strong> In this experimental study, 40 pregnant Wistar rats were randomly divided into 5 groups, including: control, UPI, UPI+GA100, UPI+GA200and UPI+GA400. For IUGR induction, anterior uterine artery occlusion surgery was carried out on gestation day (GD) 18. From GD15, GA was administrated orally, in 100, 200 and 400 mg/kg BW doses until the birth of their neonates. Spatial and working memories are analyzed by Morris water maze and Y maze at postnatal day (PND) 30, respectively. Then, BDNF cerebral cortex level was estimated using ELISA technique.The data were analyzed through ANOVA and Tukey Post hoc in SPSS software version 16.<br> <strong>Results: </strong>A significant decrease was observed in spatial and working memories and BDNF content in entorhinal cortex of UPI group in comparison with the control group (<em>p</em>˂0.05<em>)</em>. On the other hand, GA-treated groups showed a significant increase in BDNF content and amelioration of spatial and working memories (<em>p</em>˂0.05<em>)</em>.<br> <strong>Conclusion:</strong> Fetal growth restrictionafter UPI by decreasingBDNFlevel in entorhinal cortex caused memory deficits in rat&rsquo;s model. Moreover, neuroprotective effects of GA lead to increased BDNF content and ameliorate cognitive deficits in UPI model.<br> &nbsp; جریان خون جفتی, فاکتورنوروتروفیک مشتق از مغز, گالیک‌اسید, قشر انتورینال, موش صحرایی Placental Circulation, Brain Derived Neurotrophic Factor, Gallic acid, Entorhinal Cortex, Rat. 1864 1876 http://jssu.ssu.ac.ir/browse.php?a_code=A-10-3800-1&slc_lang=fa&sid=1 Zahra Esfandiari زهرا اسفندیاری zahra.esfandiry@yahoo.com 0000-0003-4563-1853 No Department of Biology, College of Sciences, Shiraz Branch, Islamic Azad University گروه زیست شناسی، دانشکده علوم، واحد شیراز، دانشگاه آزاد اسلامی، شیراز Mohammad Amin Edalatmanesh محمد امین عدالت منش amin.edalatmanesh@gmail.com 0000-0002-7936-1145 Yes Department of Biology, College of Sciences, Shiraz Branch, Islamic Azad University گروه زیست شناسی، دانشکده علوم، واحد شیراز، دانشگاه آزاد اسلامی، شیراز