The Journal of Shahid Sadoughi University of Medical Sciences
مجله علمي پژوهشي دانشگاه علوم پزشكي شهید صدوقی يزد
JSSU
Medical Sciences
http://jssu.ssu.ac.ir
20
journal20
2228-5741
2228-5733
fa
jalali
1399
3
1
gregorian
2020
6
1
28
2
online
1
fulltext
fa
بررسی اثر هیپوترمی ناشی از JZL-184 بر روی اختلال توان عضلانی و حسی - حرکتی در مدل ایسکمی دائمی شریان مغزی میانی در موش سوری نر
Effect of Hypothermia by JZL-184 on Muscle Strength and Sensory-Motor Dysfunction in Permanent Middle Cerebral Artery Ischemia Model in Male Mice
فیزیولوژی
Physiology
پژوهشي
Original article
<div style="text-align: justify;"><strong><span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;">مقدمه:</span></span></span></strong> <span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;">در حال حاضر، روش درمانی مؤثری برای سکته­ مغزی وجود ندارد. شواهد بالینی قوی برای فواید هیپوترمی در محافظت نورونی وجود دارد،</span></span></span> <span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;">از</span></span></span> <span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;">این</span></span></span> <span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;">رو،</span></span></span> <span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;">مطالعه</span></span></span> <span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;">حاضر</span></span></span> <span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;">با</span></span></span> <span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;">هدف</span></span></span> <span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;">تعیین</span></span></span> <span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;">تأثیر</span></span></span> <span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;">هیپوترمی</span></span></span> <span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;">خفیف</span></span></span> <span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;">بهصورت</span></span></span> <span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;">غیرتهاجمی توسط </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:Times New Roman,serif;"><span style="font-size:10.0pt;">JZL-184</span></span></span></span><span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;"> بر</span></span></span> <span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;">عملکرد رفتاری در موش­های</span></span></span> <span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;">مبتلا</span></span></span> <span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;">به</span></span></span> <span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;">سکته</span></span></span> <span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;">مغزی</span></span></span> <span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;">انجام</span></span></span> <span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;">شد.</span></span></span><br>
<strong><span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;">روش بررسی:</span></span></span></strong><span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;"> این مطالعه تجربی بر روی</span></span></span> <span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;">40 سر موش سورینر در 5 گروه با وزن 30 </span></span></span><span style="color:black;"><span style="font-family:Sakkal Majalla;"><span style="font-size:12.0pt;">–</span></span></span><span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;"> 25 گرم انجام شد. گروه­ها بهترتیب: 1-گروه سالم 2- گروه کنترل 3 </span></span></span><span style="color:black;"><span style="font-family:Sakkal Majalla;"><span style="font-size:12.0pt;">–</span></span></span><span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;"> گروه سکته­ مغزی + حلال</span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:Times New Roman,serif;"><span style="font-size:10.0pt;"> DMSO</span></span></span></span><span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;"> 4-</span></span></span> <span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;">گروه سکته ­مغزی+ آسپرین با</span></span></span> <span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;">دوز </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:Times New Roman,serif;"><span style="font-size:10.0pt;">mg/kg)</span></span></span></span><span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;"> 40) 5- گروه سکته­ مغزی+ </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:Times New Roman,serif;"><span style="font-size:10.0pt;">JZL-184</span></span></span></span><span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;"> با دوز</span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:Times New Roman,serif;"><span style="font-size:10.0pt;">mg/kg)</span></span></span></span><span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;">16) (8=</span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:Times New Roman,serif;"><span style="font-size:10.0pt;">n</span></span></span></span><span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;">) بودند. در خصوص گروههای 4،3 و 5 داروها بلافاصله بعد از ایجاد سکته ­مغزی</span></span></span> <span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;">بهصورت داخل صفاقی تزریق شدند. قبل از القا سکته (زمان صفر) و بعد از القا سکته ­مغزی در ساعات 5، 24 و 48 میزان درجه حرارت بدن، آزمون­های رفتاری شامل، توان عضلانی و اختلال حسی </span></span></span><span style="color:black;"><span style="font-family:Sakkal Majalla;"><span style="font-size:12.0pt;">–</span></span></span><span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;"> حرکتی بررسی شد. دادهها با استفاده از</span></span></span> <span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;">نرمافزار</span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:Cambria,serif;"><span style="font-size:10.0pt;">version 21</span></span></span></span> <span dir="LTR"><span style="color:black;"><span style="font-family:Times New Roman,serif;"><span style="font-size:10.0pt;">SPSS </span></span></span></span><span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;"> و</span></span></span> <span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;">آزمون آنالیز واریانس دو طرفه</span></span></span> <span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;">مورد تجزیه و تحلیل قرار </span></span></span><span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;">گرفتند</span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:Times New Roman,serif;"><span style="font-size:10.0pt;">(P ≤ 0.05)</span></span></span></span> <span dir="LTR"><span style="color:black;"><span style="font-family:Times New Roman,serif;"><span style="font-size:10.0pt;">.</span></span></span></span><span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;"></span></span></span><br>
<strong><span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;">نتایج:</span></span></span></strong> <span dir="LTR"><span style="color:black;"><span style="font-family:Times New Roman,serif;"><span style="font-size:10.0pt;">JZL-184</span></span></span></span><span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;"> باعث کاهش درجه حرارت در ساعات 5، 24 و 48 نسبت به گروه کنترل و سالم </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:Times New Roman,serif;"><span style="font-size:10.0pt;">(p<0.001)</span></span></span></span><span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;"> شد</span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:Times New Roman,serif;"><span style="font-size:10.0pt;">.</span></span></span></span><span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;"> تزریق </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:Times New Roman,serif;"><span style="font-size:10.0pt;">JZL-184</span></span></span></span><span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;"> و آسپرین باعث بهبود توان عضلانی و عملکرد حسی-حرکتی </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:Times New Roman,serif;"><span style="font-size:10.0pt;">(p<0.001)</span></span></span></span><span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;"> نسبت به گروه کنترل گردید. آسپرین نیز آزمون­های رفتاری را نسبت به گروه کنترل بهبود بخشیده </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:Times New Roman,serif;"><span style="font-size:10.0pt;">(p<0.01)</span></span></span></span><span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;"> اما روی درجه حرارت بدن نسبت به گروه سالم در زمان 48 اثری نشان نداد. نمرات آزمون</span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:Times New Roman,serif;"><span style="font-size:10.0pt;">­</span></span></span></span><span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;">های رفتاری در زمان 48 در مورد </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:Times New Roman,serif;"><span style="font-size:10.0pt;">JZL-184</span></span></span></span><span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;"> همانند گروه سالم شده. </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:Times New Roman,serif;"><span style="font-size:10.0pt;"></span></span></span></span><br>
<strong><span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;">نتیجهگیری:</span></span></span></strong> <span dir="LTR"><span style="color:black;"><span style="font-family:Times New Roman,serif;"><span style="font-size:10.0pt;">JZL-184</span></span></span></span><span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;"> احتمالاً توانسته است با ایجاد هیپوترمی، ناشی از اثرات آگونیستی گیرنده کانابینوئید1</span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:Times New Roman,serif;"><span style="font-size:10.0pt;">(CB1)</span></span></span></span><span style="color:black;"><span style="font-family:B Nazanin;"><span style="font-size:12.0pt;"> باعث بهبود عملکرد نورونی شده و در نتیجه، توان عضلانی و عملکرد حسی-حرکتی را بعد از ایسکمی مغزی بهبود دهد.</span></span></span></div>
<strong>Introduction:</strong> Currently, there is no effective and comprehensive treatment for ischemic stroke. There is strong clinical evidence for the benefits of hypothermia in neuroprotection. Therefore, the present study aimed to determine the effect of mild non-invasive hypothermia by JZL-184 on behavioral improvement in stroke rats.<br>
<strong>Methods:</strong> This study was performed on 5 groups of male mice weighing 25-30 g. The groups were as follows: 1- Healthy group 2- Control group (Stroke) 3- Stroke + DMSO solvent 4- Stroke + Aspirin (40mg /kg) 5- Stroke + JZL-184 (16mg / kg) (n = 8 per group). The drugs were injected intraperitoneally immediately after the stroke. At the times before (time zero) and at 5, 24 and 48 h after stroke induction, body temperature, behavioral testing, including muscle strength and sensory-motor dysfunction were measured. Data were analyzed by SPSS version 18 software and Two-way ANOVA test (P ≤ 0.05).<br>
<strong>Results:</strong> JZL-184 decreased body temperature at 5, 24 and 48 hours compared to intact and control groups (p <0.001). Injection JZL-184 and Aspirin improved muscle strength and sensory-motor function (p <0.001) compared to the control group. Aspirin also improved behavioral tests compared to the control group (p <0.01), but did not show any effect on the body temperature compared to the intact group at time 48. Only in JZL-184 group, the behavioral tests score was similar to the intact group at the 48 h after stroke.<br>
<strong>Conclusion:</strong> JZL-184 may have been able to improve neuronal function by hypothermia induced by the agonist effects of cannabinoid receptor 1 (CB1), thereby improving muscle strength and sensory-motor function after cerebral ischemia.<span dir="RTL"></span>
سکتهمغزی, JZL-184, هیپوترمی, ایسکمی
Stroke, JZL-184, Hypothermia, Ischemia.
2351
2362
http://jssu.ssu.ac.ir/browse.php?a_code=A-10-4167-1&slc_lang=fa&sid=1
Mohammad Reza
Rahmani
محمدرضا
رحمانی
drrahmani.1347@gmail.com