fa بیماری کبد چرب مرتبط با اختلال متابولیک و استئاتوهپاتیت مرتبط با اختلال متابولیک: مروری بر پاتوژنز و اهداف دارویی بالقوه medicine, paraclinic medicine, paraclinic مروري Review <div style="text-align: justify;"><span style="font-size:11pt"><span style="line-height:normal"><span style="direction:rtl"><span style="unicode-bidi:embed"><span calibri="" style="font-family:"><strong><span lang="FA" style="font-size:9.0pt"><span b="" style="font-family:" zar="">سابقه و هدف:</span></span> </strong><span lang="PS-AF" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">بیماری کبد چرب مرتبط با اختلال متابولیک (</span></span><span dir="LTR" style="font-size:9.0pt"><span new="" roman="" style="font-family:" times="">MAFLD</span></span><span lang="PS-AF" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">) از شایع</span></span><span lang="FA" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">‌</span></span><span lang="PS-AF" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">ترین بیماری</span></span><span lang="FA" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">‌</span></span><span lang="PS-AF" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">های کبدی است که </span></span><span lang="FA" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">به</span></span><span lang="PS-AF" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">واسطه رسوب چربی در هپاتوسیت</span></span><span lang="FA" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">‌</span></span><span lang="PS-AF" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">ها ایجاد می</span></span><span lang="FA" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">‌</span></span><span lang="PS-AF" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">شود. با پیشرفت استئاتوز به</span></span><span lang="FA" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">‌</span></span><span lang="PS-AF" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">سمت نکروز و التهاب سلو</span></span><span lang="FA" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">ل‌</span></span><span lang="PS-AF" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">های کبدی، استئاتوهپاتیت مرتبط با اختلال متابولیک (</span></span><span dir="LTR" style="font-size:9.0pt"><span new="" roman="" style="font-family:" times="">MASH</span></span><span lang="PS-AF" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">) رخ می</span></span><span lang="FA" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">‌</span></span><span lang="PS-AF" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">دهد. مقاومت به انسولین و چاقی از عوامل مهم در پاتوژنز</span></span> <span lang="PS-AF" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">کبد چرب محسوب می</span></span><span lang="FA" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">‌</span></span><span lang="PS-AF" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">شوند. آسیب اکسیداتیو کبد و به</span></span><span lang="FA" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">‌</span></span><span lang="PS-AF" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">هم</span></span><span lang="FA" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">‌</span></span><span lang="PS-AF" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">خوردن میکروفلور روده نیز در پیشرفت بیماری دخیل هستند. در حال حاضر داروی اختصاصی برای این بیماری وجود ندارد و اغلب اصلاح سبک زندگی توصیه می</span></span><span lang="FA" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">‌</span></span><span lang="PS-AF" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">شود. هدف از مطالعه حاضر</span></span><span lang="FA" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">،</span></span><span lang="PS-AF" style="font-size:9.0pt"><span b="" lotus="" style="font-family:"> مرور اهداف دارویی بالقوه در درمان کبد چرب می</span></span><span lang="FA" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">‌</span></span><span lang="PS-AF" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">باشد.</span></span><span lang="FA" style="font-size:9.0pt"><span style="font-family:"B Lotus""></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 calibri="" style="font-family:"><strong><span lang="PS-AF" style="font-size:9.0pt"><span b="" style="font-family:" zar="">مواد و رو</span></span><span lang="FA" style="font-size:9.0pt"><span b="" style="font-family:" zar="">ش‌</span></span></strong><span lang="PS-AF" style="font-size:9.0pt"><strong><span b="" style="font-family:" zar="">ها:</span></strong><span b="" lotus="" style="font-family:"><strong> </strong>در مقاله حاضر با مطالعه کارآزمایی</span></span><span lang="FA" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">‌</span></span><span lang="PS-AF" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">های بالینی ثبت</span></span><span lang="FA" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">‌</span></span><span lang="PS-AF" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">شده در پایگاه بین</span></span><span lang="FA" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">‌</span></span><span lang="PS-AF" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">المللی </span></span><span dir="LTR" style="font-size:9.0pt"><span new="" roman="" style="font-family:" times="">ICTRP</span></span><span lang="PS-AF" style="font-size:9.0pt"><span b="" lotus="" style="font-family:"> سازمان بهداشت جهانی و مقالات چا‌‌‌پ</span></span><span lang="FA" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">‌</span></span><span lang="PS-AF" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">شده در پایگاه</span></span><span lang="FA" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">‌</span></span><span lang="PS-AF" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">های اطلاعاتی</span></span><span dir="LTR" style="font-size:9.0pt"><span new="" roman="" style="font-family:" times="">PubMed </span></span><span lang="PS-AF" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">،</span></span><span dir="LTR" style="font-size:9.0pt"><span new="" roman="" style="font-family:" times="">Google Scholar </span></span><span lang="PS-AF" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">، </span></span><span dir="LTR" style="font-size:9.0pt"><span new="" roman="" style="font-family:" times="">ISI Web of Science</span></span><span lang="PS-AF" style="font-size:9.0pt"><span b="" lotus="" style="font-family:"> و </span></span><span dir="LTR" style="font-size:9.0pt"><span new="" roman="" style="font-family:" times="">Scopus</span></span><span lang="PS-AF" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">، اهداف دارویی مهم در بیماری کبد چرب و استئاتوهپاتیت با تمرکز بر یافته</span></span><span lang="FA" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">‌</span></span><span lang="PS-AF" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">های جدید، بررسی شده است.</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 calibri="" style="font-family:"><span lang="PS-AF" style="font-size:9.0pt"><strong><span b="" style="font-family:" zar="">نتایج:</span></strong><span b="" lotus="" style="font-family:"> گیرنده فعال</span></span><span lang="FA" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">‌</span></span><span lang="PS-AF" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">کننده پروکسیزوم (</span></span><span dir="LTR" style="font-size:9.0pt"><span new="" roman="" style="font-family:" times="">PPAR</span></span><span lang="PS-AF" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">)،</span></span> <span lang="PS-AF" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">پپتید-۱</span></span> <span lang="PS-AF" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">شبه گلوکاگون (</span></span><span dir="LTR" style="font-size:9.0pt"><span new="" roman="" style="font-family:" times="">GLP-1</span></span><span lang="PS-AF" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">)، گیرنده فارنزوئید </span></span><span dir="LTR" style="font-size:9.0pt"><span new="" roman="" style="font-family:" times="">X</span></span><span lang="PS-AF" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">، استاتین</span></span><span lang="FA" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">‌</span></span><span lang="PS-AF" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">ها، واسطه</span></span><span lang="FA" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">‌</span></span><span lang="PS-AF" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">های دخیل در فیبروز و التهاب، عوامل کاهنده وزن و پروبیوتیک</span></span><span lang="FA" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">‌</span></span><span lang="PS-AF" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">ها جز</span></span><span lang="FA" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">ء</span></span><span lang="PS-AF" style="font-size:9.0pt"><span b="" lotus="" style="font-family:"> اهداف اصلی مورد مداخله در بیماری کبد چرب بو</span></span><span lang="FA" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">ده‌</span></span><span lang="PS-AF" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">اند.</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 calibri="" style="font-family:"><strong><span lang="FA" style="font-size:9.0pt"><span b="" style="font-family:" zar="">نتیجه‌گیری:</span></span></strong><span lang="PS-AF" style="font-size:9.0pt"><span b="" lotus="" style="font-family:"> داروهای کاهنده وزن نظیر ارلیستات و آنالوگ</span></span><span lang="FA" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">‌</span></span><span lang="PS-AF" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">های </span></span><span dir="LTR" style="font-size:9.0pt"><span new="" roman="" style="font-family:" times="">GLP-1</span></span> <span lang="PS-AF" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">به </span></span><span lang="PS-AF" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">خصوص در افراد چاق مبتلا به کبد چرب اثرات خوبی داشت</span></span><span lang="FA" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">ه‌</span></span><span lang="PS-AF" style="font-size:9.0pt"><span b="" lotus="" style="font-family:">اند.</span></span> <span lang="PS-AF" style="font-size:9.0pt"><span b="" lotus="" style="font-family:"><span style="letter-spacing:-.1pt">همچنین بهبود مقاومت به انسولین و هیپرلیپیدمی توسط آگونیست</span></span></span><span lang="FA" style="font-size:9.0pt"><span b="" lotus="" style="font-family:"><span style="letter-spacing:-.1pt">‌</span></span></span><span lang="PS-AF" style="font-size:9.0pt"><span b="" lotus="" style="font-family:"><span style="letter-spacing:-.1pt">های </span></span></span><span dir="LTR" style="font-size:9.0pt"><span new="" roman="" style="font-family:" times=""><span style="letter-spacing:-.1pt">PPAR</span></span></span><span lang="PS-AF" style="font-size:9.0pt"><span b="" lotus="" style="font-family:"><span style="letter-spacing:-.1pt">، آنالو</span></span></span><span lang="FA" style="font-size:9.0pt"><span b="" lotus="" style="font-family:"><span style="letter-spacing:-.1pt">گ‌</span></span></span><span lang="PS-AF" style="font-size:9.0pt"><span b="" lotus="" style="font-family:"><span style="letter-spacing:-.1pt">های </span></span></span><span dir="LTR" style="font-size:9.0pt"><span new="" roman="" style="font-family:" times=""><span style="letter-spacing:-.1pt">GLP-1</span></span></span><span style="font-size:9.0pt"><span b="" lotus="" style="font-family:"><span style="letter-spacing:-.1pt"> و استاتین</span></span></span><span lang="FA" style="font-size:9.0pt"><span b="" lotus="" style="font-family:"><span style="letter-spacing:-.1pt">‌</span></span></span><span lang="PS-AF" style="font-size:9.0pt"><span b="" lotus="" style="font-family:"><span style="letter-spacing:-.1pt">ها پتانسیل درمانی خوبی نشان داد</span></span></span><span lang="FA" style="font-size:9.0pt"><span b="" lotus="" style="font-family:"><span style="letter-spacing:-.1pt">ه‌</span></span></span><span lang="PS-AF" style="font-size:9.0pt"><span b="" lotus="" style="font-family:"><span style="letter-spacing:-.1pt">اند</span>.</span></span></span></span></span></span></span></div> <div style="text-align: justify;"><span style="font-family:Times New Roman;"><span style="font-size:12pt"><span style="unicode-bidi:embed"><span new="" roman="" times=""><b>Background:</b> Metabolic dysfunction-associated fatty liver disease (MAFLD) is one of the most common liver diseases that results from excess fat accumulation in the hepatocytes. The progression of steatosis to hepatocellular necrosis and inflammation leads to metabolic-associated steatohepatitis (MASH). Insulin resistance and obesity have significant roles in the disease process. Oxidative damage to hepatocytes and gut microflora dysbiosis may also contribute to the progression of fatty liver disease. There is currently no specific medication for MAFLD, and usually, lifestyle modifications are recommended. This study aimed to review the potential pharmacological targets for MAFLD.<span dir="RTL" style="font-family:"B Lotus"" lang="PS-AF"></span></span></span></span><br> <span style="font-size:12pt"><span style="unicode-bidi:embed"><span new="" roman="" times=""><b>Materials and Methods:</b> In this paper, we studied the primary pharmacological targets for MAFLD and MASH, focusing on current evidence from clinical trials registered on the WHO International Clinical Trials Registry Platform (ICTRP) and published articles in PubMed, Google Scholar, ISI Web of Science, and Scopus databases.</span></span></span><br> <span style="font-size:12pt"><span style="unicode-bidi:embed"><span new="" roman="" times=""><b>Results: </b>The&nbsp;peroxisome proliferator-activated receptors&nbsp;(PPARs), glucagon-like peptide-1 (GLP-1),&nbsp;farnesoid X receptor, statins, mediators&nbsp;of&nbsp;fibrosis and inflammation, weight loss agents, and probiotics were the primary targets in the treatment of fatty liver disease.</span></span></span><br> <span style="font-size:12pt"><span style="unicode-bidi:embed"><span new="" roman="" times=""><b>Conclusion:</b> The drugs decreasing body weight, such as orlistat and GLP-1 analogs, have beneficial effects in obese patients with fatty liver disease. Moreover, insulin-sensitizers and lipid-lowering agents like PPAR agonists, GLP-1 analogs, and statins are valuable in this condition.</span></span></span></span></div> بیماری کبد چرب, استئاتوهپاتیت, پاتوژنز, اهداف دارویی Fatty liver disease, Steatohepatitis, Pathogenesis, Drug targets 605 616 http://feyz.kaums.ac.ir/browse.php?a_code=A-10-4231-1&slc_lang=fa&sid=1 Samaneh Olapour سمانه اولی پور olapour.s@gmail.com 2900319475328460039740 2900319475328460039740 No Herbal Pharmacology Research Center, Faculty of Medicine, Islamic Azad University, Tehran, I.R Iran. مرکز تحقیقات فارماکولوژی گیاهان دارویی، دانشکده پزشکی، دانشگاه آزاد اسلامی، تهران، ایران Hamid Yaghooti حمید یاقوتی hmdyaghooti@gmail.com 2900319475328460039741 2900319475328460039741 Yes Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, I.R Iran. گروه بیوشیمی بالینی، دانشکده علوم پزشکی، دانشگاه تربیت مدرس، تهران، ایران