Iranian Journal of Diabetes and Lipid Disorders
مجله دیابت و متابولیسم ایران
ijdld
Medical Sciences
http://ijdld.tums.ac.ir
1
admin
2345-4008
2345-4016
000
000
000
000
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fa
jalali
1403
9
1
gregorian
2024
12
1
24
5
online
1
fulltext
fa
ارزیابی اثرات حفاظتی دی متیل فومارات بر سمیّت کبدی و کلیوی موشهای دیابتی ناشی از تزریق آلوکسان از مسیرهای التهاب و استرس اکسیداتیو
The Protective Effects of Dimethyl Fumarate on Hepato-Renal Toxicity in Alloxan-Induced Diabetic Mice Through Oxidative Stress and Inflammation Signaling Pathways
تخصصي
Special
پژوهشي
Research
<span style="font-size:11pt"><span style="tab-stops:right 0cm"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="line-height:107%"><span style="font-family:"Calibri",sans-serif"><b><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Lotus""><span style="letter-spacing:-.3pt">مقدمه:</span></span></span></b><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Lotus""><span style="letter-spacing:-.3pt"> دیابت شایعترین بیماری متابولیک ناشی از کمبود نسبی ترشح یا عملکرد انسولین است. دیابت میتواند منجر به عوارض گوناگونی در بدن از جمله آسیب کبدی و کلیوی شود. هدف از این مطالعه، ارزیابی اثرات حفاظتی دی متیل فومارات بر سمیّت کبدی و کلیوی موشهای دیابتی ناشی از تزریق آلوکسان از مسیرهای التهاب و استرس اکسیداتیو بود.</span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Lotus""><span style="letter-spacing:-.3pt"></span></span></span></span></span></span></span></span></span><br>
<span style="font-size:11pt"><span style="tab-stops:right 0cm"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="line-height:107%"><span style="font-family:"Calibri",sans-serif"><b><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Lotus""><span style="letter-spacing:-.3pt">روشها</span></span></span></b><b><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Lotus""><span style="letter-spacing:-.4pt">:</span></span></span></b><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Lotus""><span style="letter-spacing:-.4pt"> موش</span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"Cambria",serif"><span style="letter-spacing:-.4pt"></span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Lotus""><span style="letter-spacing:-.4pt">های ماده از نژاد (</span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="letter-spacing:-.4pt">C57BL/6</span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Lotus""><span style="letter-spacing:-.4pt">) با تزریق داخل صفاقی آلوکسان مونوهیدرات محلول در سرم فیزیولوژی (به میزان 120 میلیگرم به ازای هر کیلوگرم وزن بدن) در 3 روز متوالی دیابتی شدند. موشها به 7 گروه 5 تایی شامل گروههای دریافت </span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"Cambria",serif"><span style="letter-spacing:-.4pt"></span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Lotus""><span style="letter-spacing:-.4pt">کنندۀ آلوکسان و دی متیل فومارات دستهبندی شدند. موشهای دیابتی نوع اوّل با 3 دوز از دی متیل فومارات (بهترتیب،</span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="letter-spacing:-.4pt">mg/kg </span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Lotus""><span style="letter-spacing:-.4pt"> 20، 40 و 80) بهمدت 21 روز تحت درمان قرار گرفتند. سپس، آزمون</span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"Cambria",serif"><span style="letter-spacing:-.4pt"></span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Lotus""><span style="letter-spacing:-.4pt">های اختصاصی جهت ارزیابی پارامترهای بیوشیمیایی خون، نشانگرهای استرس اکسیداتیو، بیان ژنهای التهابی (</span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="letter-spacing:-.4pt">TNF-α</span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Lotus""><span style="letter-spacing:-.4pt">، </span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="letter-spacing:-.4pt">IL-6</span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Lotus""><span style="letter-spacing:-.4pt"> و </span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="letter-spacing:-.4pt">NF-kB</span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Lotus""><span style="letter-spacing:-.4pt">) و ژنهای مرتبط با پیشگیری از تشدید استرس اکسیداتیو و عوارض ناشی از دیابت (شامل بیان دو ژن </span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="letter-spacing:-.4pt">Sirt-1</span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Lotus""><span style="letter-spacing:-.4pt"> (سیرتوئین) و </span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="letter-spacing:-.4pt">Nrf2</span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Lotus""><span style="letter-spacing:-.4pt">) به کمک روش ریل</span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"Cambria",serif"><span style="letter-spacing:-.4pt"></span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Lotus""><span style="letter-spacing:-.4pt">تایم </span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="letter-spacing:-.4pt">PCR</span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Lotus""><span style="letter-spacing:-.4pt"> انجام شد. در پایان، مشاهدات هیستوپاتولوژیکی در دو بافت کبد و کلیه موش</span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"Cambria",serif"><span style="letter-spacing:-.4pt"></span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Lotus""><span style="letter-spacing:-.4pt">ها هم ارزیابی گردید.</span></span></span></span></span></span></span></span></span><br>
<span style="font-size:11pt"><span style="tab-stops:right 0cm"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="line-height:107%"><span style="font-family:"Calibri",sans-serif"><b><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Lotus""><span style="letter-spacing:-.3pt">یافتهها:</span></span></span></b><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Lotus""><span style="letter-spacing:-.3pt"> تجویز دی متیل فومارات به موش</span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"Cambria",serif"><span style="letter-spacing:-.3pt"></span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Lotus""><span style="letter-spacing:-.3pt">های دیابتی در یک رفتار وابسته به دوز منجر به کاهش معنادار سطوح گلوکز، </span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="letter-spacing:-.3pt">AST</span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Lotus""><span style="letter-spacing:-.3pt">، </span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="letter-spacing:-.3pt">ALT</span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Lotus""><span style="letter-spacing:-.3pt"> و کراتنین خون در مقایسه با گروه شاهد شد. تغییرات هیستوپاتولوژیک کمتر و کاهش بیشتری در سطح شاخصهای استرس اکسیداتیو در کلیه و کبد گروه</span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"Cambria",serif"><span style="letter-spacing:-.3pt"></span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Lotus""><span style="letter-spacing:-.3pt">های تیمارشده با دی متیل فومارات در مقایسه با موشهای دیابتی مشاهده شد (001/0</span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="letter-spacing:-.3pt">P< </span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Lotus""><span style="letter-spacing:-.3pt">). مواجهه با دی متیل فومارات به شکل معناداری موجب افزایش بیان ژنهای </span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="letter-spacing:-.3pt">Sirt-1</span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Lotus""><span style="letter-spacing:-.3pt"> و </span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="letter-spacing:-.3pt">Nrf2</span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Lotus""><span style="letter-spacing:-.3pt"> و کاهش بیان ژنهای دخیل در بروز التهاب نسبت به گروه دیابتی در هر دو بافت کبد و کلیه شد.<i></i></span></span></span></span></span></span></span></span></span><br>
<span style="font-size:11pt"><span style="tab-stops:right 0cm"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="line-height:107%"><span style="font-family:"Calibri",sans-serif"><b><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Lotus""><span style="letter-spacing:-.3pt">نتیجهگیری: </span></span></span></b><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Lotus""><span style="letter-spacing:-.3pt">تجویز دی متیل فومارات موجب بهبود شاخص</span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"Cambria",serif"><span style="letter-spacing:-.3pt"></span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Lotus""><span style="letter-spacing:-.3pt">های بیوشیمیایی خون، استرس اکسیداتیو، هیستوپاتولوژی وتعدیل مسیر بیان دو ژن </span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="letter-spacing:-.3pt">Sirt-1</span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Lotus""><span style="letter-spacing:-.3pt"> و </span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="letter-spacing:-.3pt">Nrf2</span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Lotus""><span style="letter-spacing:-.3pt"> در دو بافت کلیه و کبد موش</span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"Cambria",serif"><span style="letter-spacing:-.3pt"></span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Lotus""><span style="letter-spacing:-.3pt">های دیابتی شد.</span></span></span></span></span></span></span></span></span><br>
<span style="font-size:11pt"><span style="line-height:92%"><span style="tab-stops:right 0cm"><span style="font-family:"Calibri",sans-serif"><b><span style="line-height:92%"><span style="font-family:"Times New Roman",serif">Background:</span></span></b><span style="line-height:92%"><span style="font-family:"Times New Roman",serif"> Despite advances in diabetes-related treatments, the effects of the disease have not yet been adequately reversed or prevented in patients. Therefore, there is an urgent need to develop more effective medication-assisted treatments in this field.</span></span></span></span></span></span><br>
<span style="font-size:11pt"><span style="line-height:92%"><span style="tab-stops:right 0cm"><span style="font-family:"Calibri",sans-serif"><b><span style="line-height:92%"><span style="font-family:"Times New Roman",serif">Methods:</span></span></b><span style="line-height:92%"><span style="font-family:"Times New Roman",serif"> In this study, type 1 diabetes mice models was established using multiple low-dose alloxan, and the diabetic mice were treated with three doses of dimethyl fumarate (DMF) i.e low, medium, and high viz. 20, 40 and 80 mg/kg, respectively for a period of 21 days. Then, specific test were done to evaluate blood biochemical parameters, oxidative stress markers, inflammatory genes expression, and histopathological changes in the mice kidney and liver. </span></span></span></span></span></span><br>
<span style="font-size:11pt"><span style="line-height:92%"><span style="tab-stops:right 0cm"><span style="font-family:"Calibri",sans-serif"><b><span style="line-height:92%"><span style="font-family:"Times New Roman",serif">Results:</span></span></b><span style="line-height:92%"><span style="font-family:"Times New Roman",serif"> The obtained results showed remarkably improved anti-diabetic, hepato-renal-protective, and oxidative stress indexes of DMF in alloxan-induced diabetic mice (P< 0.001). Treated mice with DMF demonstrated a noteworthy decrease in blood glucose levels when compared with diabetic group (P< 0.001). Diabetic liver and kidney tissues showed marked dilation of bile ducts, tubules, infiltration, and inflammation. On the contrary, the histological features of the treated mice with DMF improve as shown by normal size of glomerular capillaries along with decrease in less dilatation of ducts in comparison with diabetic mice. The real-time quantitative PCR results indicated that DMF injection decreased the alloxan-induced increase of significant elevations in mRNA levels of pro-inflammatory cytokines levels in both kidney and liver tissues. Meanwhile, mice treated with DMF showed an increase in Sirt1 and Nrf2 expression in comparison to diabetic group.</span></span></span></span></span></span><br>
<span style="font-size:11pt"><span style="line-height:92%"><span style="tab-stops:right 0cm"><span style="font-family:"Calibri",sans-serif"><b><span style="line-height:92%"><span style="font-family:"Times New Roman",serif">Conclusion:</span></span></b><span style="line-height:92%"><span style="font-family:"Times New Roman",serif"> In conclusion, it can be concluded that DMF treatment provides hepato-renal protective effects on alloxan-induced diabetic mice model by attenuating ROS inflammatory pathways.</span></span></span></span></span></span><br>
دیابت, آلوکسان, دی متیل فومارات, استرس اکسیداتیو, پاسخهای ضدالتهابی, اثرات حفاظت از بافت کبدی-کلیوی
Diabetes, Alloxan, Dimethyl fumarate, Oxidative stress, Anti-inflammatory responses, Hepato-renal-protective effects.
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http://ijdld.tums.ac.ir/browse.php?a_code=A-10-2101-1&slc_lang=fa&sid=1
Parisa
Saberi-Hasanabadi
پریسا
صابری حسن آبادی
dr.parisasaberi@gmail.com