fa فراوانی ژن پمپ های افلاکس PGP و MRPA در ایجاد مقاومت دارویی در ایزوله های بالینی لیشمانیا تروپیکا و لیشمانیا ماژور علوم سلولی و مولکولی Cell and Molecular Biology مقاله پژوهشی Original Article <span style="font-size:11pt"><span style="text-justify:kashida"><span style="text-kashida:0%"><span style="line-height:normal"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="font-family:Calibri,sans-serif"><span lang="FA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">هدف‌ این تحقیق‌ شناسایی ‌ژن‌ پمپ‌های </span></span><span dir="LTR" lang="EN-CA" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">MRPA</span></span> <span lang="FA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">و </span></span><span dir="LTR" lang="EN-CA" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">PGP</span></span> <span lang="FA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">در ‌ایزوله‌های‌ بالینی ‌لیشمانیا است. از جمله‌ی ‌این ژن‌های‌ دخیل‌ در‌ مقاومت </span></span><span lang="FA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">(</span></span><span dir="LTR" lang="EN-CA" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">MRPA</span></span><span lang="FA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">) </span></span><span dir="LTR" lang="EN-CA" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">pgpa</span></span> <span lang="FA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">و (</span></span><span dir="LTR" lang="EN-CA" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">PGP</span></span><span lang="FA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">) </span></span><span dir="LTR" lang="EN-CA" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">mdr1</span></span> <span lang="FA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">هستند، که‌ محصول‌ آنها &nbsp;به‌ عنوان‌ انتقال‌دهنده &nbsp;وابسته &nbsp;‌به</span></span>&nbsp; (<span dir="LTR" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">(ABC Transporter</span></span><span dir="LTR" lang="EN-CA" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">ATP&nbsp;</span></span><span lang="FA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">در ‌افلاکس &nbsp;‌دارو‌ از ‌سیتوزول ‌به خارج غشا نقش دارند.‌ در این‌ راستا 40 داوطلب‌ مبتلا به‌ سالک ‌‌به طور‌ اتفاقی انتخاب گردیدند.‌ ابتدا آماستیگوت ها‌ با‌‌ میکروسکوپ نوری ‌بررسی گردیدند، سپس به‌ محیط ‌کشت دو فازی اختصاصی</span></span><span dir="LTR" lang="EN-CA" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">NNN</span></span><span lang="FA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">‌ </span></span><span lang="FA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">تلقیح شدند.‌&lrm;‌ </span></span><span dir="LTR" lang="EN-CA" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">DNA</span></span><span lang="FA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">‌‌ ها به‌ روش فنل-کلروفرم ‌استخراج شدند و‌ با‌ پرایمرهای ‌اختصاصی ناحیه </span></span><span dir="LTR" lang="EN-CA" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">ITS</span></span> <span lang="FA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">عامل‌ ایجاد‌ زخم ‌تعیین ‌هویت‌ گردیدند. سپس فراوانی ‌دو ‌پمپ‌ دخیل ‌در‌ مقاومت‌ دارویی‌ به ‌کمک </span></span><span dir="LTR" lang="EN-CA" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">PCR</span></span><span lang="FA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">‌ </span></span><span lang="FA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">&nbsp;بررسی‌ شد. در ‌این‌ مطالعه‌ ژن </span></span><span dir="LTR" lang="EN-CA" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">mdr1</span></span> <span lang="FA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">که ‌پیش ‌از‌ این ‌در‌ سویه‌های ‌آزمایشگاهی ‌مقاوم‌‌&lrm;‌ شده‌ به ‌ دارو‌ نشان ‌داده ‌شده بود، ‌نسبت به </span></span><span dir="LTR" lang="EN-CA" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">pgpa</span></span> &nbsp;<span lang="FA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">فراوانی‌ بیشتری ‌را دارا‌&nbsp; بودند ‌که‌ یکی ‌از ‌دلایل ‌افزایش را می توان به‌ علت‌ حضور‌ پمپ </span></span><span dir="LTR" lang="EN-CA" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">MDR</span></span> <span lang="FA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">در‌سطح غشای‌ پلاسمایی اشاره‌ کرد‌، که‌ مواد‌‌ و دارو‌ را از‌‌ لایه های ‌‌داخلی‌ غشای دو ‌لایه ‌لیپیدی به ‌لایه های‌ خارجی انتقال‌ &nbsp;می‌دهد و‌ غلظت ‌دارو را‌ در‌ داخل‌ سلول ‌کم می‌کند و باعث مقاومت‌ دارویی ‌می‌شود در حالی‌که‌ پمپ </span></span><span dir="LTR" lang="EN-CA" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">MRPA</span></span> <span lang="FA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">در‌ غشا اندامک‌‌ سلولی است.</span></span><span dir="LTR" lang="EN-CA" style="font-size:9.0pt"><span new="" roman="" style="font-family:" times=""><span style="color:black"></span></span></span></span></span></span></span></span></span></span><br /> <span style="font-size:11pt"><span style="line-height:normal"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="font-family:Calibri,sans-serif"><b><span dir="LTR" lang="EN-CA" style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"></span></span></b></span></span></span></span></span><br /> &nbsp; <span style="font-size:11pt"><span style="line-height:normal"><span style="font-family:Calibri,sans-serif"><span lang="EN-CA" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">This study aimed to identify PGP and MRPA genes in clinical isolates of <i>Leishmania</i>. The genes of pgpa (MRPA)</span></span> <span lang="EN-CA" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">and mdr1 (PGP) are involved in the drug resistance, their products act as dependent transporters of ATP (ABC Transporter) in the reflux of drugs from the cytosol to the outer space of the cell.</span></span> <span style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">Hence</span></span><span lang="EN-CA" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">, 40 volunteers with leishmaniasis were randomly selected. Firstly, Amastigotes were examined under a light microscope, then inoculated into NNN-specific biphasic culture medium. </span></span><span lang="EN-CA" style="font-size:10.0pt"><span style="background:white"><span new="" roman="" style="font-family:" times=""><span style="color:black">Deoxy ribonucleic acids</span></span></span></span> <span lang="EN-CA" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">were extracted by phenol-chloroform method and were determined by ITS-specific primers. Then the frequency of two pumps involved in &quot;drug resistance&quot; was investigated by PCR. In this study, the mdr1 gene, which had previously been shown to be present in the in vitro resistant strains, was shown to have a higher frequency of pgpas, which could be due to the presence of MDR. It transports the drug from the inner layers of the lipid bilayer membrane to the outer layers, reducing the concentration of the</span></span> <span lang="EN-CA" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">drug inside the cell and causing drug resistance, while the MRPA pump is in the membrane of the cell organelles.</span></span></span></span></span><br /> <span style="font-size:11pt"><span style="text-justify:kashida"><span style="text-kashida:0%"><span style="line-height:normal"><span style="font-family:Calibri,sans-serif"><span lang="EN" style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"></span></span></span></span></span></span></span><br /> &nbsp; انتقال دهنده ABC, ژن mdr1, ژن pgpa, گلوکانتیم, لیشمانیوز جلدی ABC transporter, cutaneous leishmaniasis, glucantim, mdr1 gene, pgpa gene 257 266 http://nbr.khu.ac.ir/browse.php?a_code=A-12-1322-2&slc_lang=fa&sid=1 Maede Parishan مائده پریشان maede_parishan@yahoo.com 10031947532846009986 10031947532846009986 Yes Microbial Biotechnology, Payame Noor University of East Tehran, Tehran, Iran بیوتکنولوژی میکروبی، دانشگاه پیام نور تهران شرق، تهران، ایران Mahmoud Nateghi محمود ناطقی 10031947532846009987 10031947532846009987 No Qom University of medical science, Health college, Qom, Iran دانشکده بهداشت، دانشگاه علوم پزشکی قم، قم، ایران