Razi Journal of Medical Sciences
مجله علوم پزشکی رازی
RJMS
Medical Sciences
http://rjms.iums.ac.ir
39
journal39
2228-7043
2228-7051
en
jalali
1401
9
1
gregorian
2022
12
1
29
9
online
1
fulltext
fa
تاثیر بیماری کبد چرب بر بیان ژنهای RXFP1 و CTGF در بافت قلبی رتهای ویستار
The Effect of Fatty Liver Disease on the Expression of RXFP1 and CTGF Genes in Cardiac Tissue of Wistar Rats
فیزیولوژی
Physiology
پژوهشي
Research
<span style="font-size:11pt"><span style="text-justify:kashida"><span style="text-kashida:0%"><span style="tab-stops:10.5pt"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="line-height:115%"><span style="font-family:Calibri,sans-serif"><b><span lang="FA" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"B Mitra""><span style="color:#0070c0">زمینه و هدف: </span></span></span></span></b><span lang="FA" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"B Mitra""><span style="color:black">کبد چرب با افزایش خطر بیماری</span></span></span></span><b><span dir="LTR" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"Times New Roman",serif"><span style="color:black"></span></span></span></span></b><span lang="FA" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"B Mitra""><span style="color:black">های قلبی عروقی و تشکیل پلاک</span></span></span></span><b><span dir="LTR" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"Times New Roman",serif"><span style="color:black"></span></span></span></span></b><span lang="FA" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"B Mitra""><span style="color:black">های آترواسکلروتیک در عروق کاروتید همراه است و تنگ شدن عروق کرونری </span></span></span></span><span lang="FA" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"B Mitra""><span style="color:black">میتواند در فاکتورهای </span></span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"Times New Roman",serif"><span style="color:black">ECM</span></span></span></span><span lang="FA" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"B Mitra""><span style="color:black"> از قبیل </span></span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"Times New Roman",serif"><span style="color:black">CTGF</span></span></span></span><span lang="FA" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"B Mitra""><span style="color:black"> و </span></span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"Times New Roman",serif"><span style="color:black">RXFP1</span></span></span></span><span lang="FA" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"B Mitra""><span style="color:black"> که در ایجاد یا عدم فیبروز نقش دارد مؤثر باشد لذا هدف بررسی تأثیر این بیماری بر دو ژن </span></span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"Times New Roman",serif"><span style="color:black">ECM</span></span></span></span><span lang="FA" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"B Mitra""><span style="color:black"> قلب است.</span></span></span></span></span></span></span></span></span></span></span></span><br>
<span style="font-size:11pt"><span style="text-justify:kashida"><span style="text-kashida:0%"><span style="tab-stops:10.5pt"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="line-height:115%"><span style="font-family:Calibri,sans-serif"><b><span lang="FA" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"B Mitra""><span style="color:#0070c0">روش کار:</span></span></span></span></b><b> </b><span lang="FA" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"B Mitra""><span style="color:black">در این مطالعه 24 سر رت نر ویستار با وزن 200 </span></span></span></span><span lang="FA" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"Times New Roman",serif"><span style="color:black">–</span></span></span></span><span lang="FA" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"B Mitra""><span style="color:black"> 250 گرم در 3 گروه کنترل، سالم و کبد چرب به صورت تصادفی تقسیم شدند. گروه کنترل همان ابتدا مطالعه قربانی و بافتبرداری انجام شد و دو گروه سالم و کبد چرب دو هفته را در شرایط یکسان سپری کردند. گروه سالم از ابتدا تا انتهای مطالعه وجود داشتند و هیچ مداخلهای را دریافت نمیکردند. موشهای گروه کبد چرب به مدت دو هفته،</span></span></span></span> <span lang="FA" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"B Mitra""><span style="color:black">روزانه،</span></span></span></span> <span lang="FA" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"B Mitra""><span style="color:black">تتراسایکلین خوراکی با دوز </span></span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"Times New Roman",serif"><span style="color:black">mg/kg</span></span></span></span><span lang="FA" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"B Mitra""><span style="color:black"> 100 دریافت کردند. 100</span></span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"Times New Roman",serif"><span style="color:black"> mg</span></span></span></span><span lang="FA" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"B Mitra""><span style="color:black"> به ازای هر 1</span></span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"Times New Roman",serif"><span style="color:black"> kg</span></span></span></span><span lang="FA" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"B Mitra""><span style="color:black"> برای 3 موش استفاده شد. تاییدیه کبد چرب را از طریق اندازهگیری آنزیم کبدی (</span></span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"Times New Roman",serif"><span style="color:black">SGPT</span></span></span></span><span lang="FA" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"B Mitra""><span style="color:black">) انجام شد. در پایان هفته دوم رتهای دو گروه قربانی شدند.</span></span></span></span></span></span></span></span></span></span></span></span><br>
<span style="font-size:11pt"><span style="text-justify:kashida"><span style="text-kashida:0%"><span style="tab-stops:10.5pt"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="line-height:115%"><span style="font-family:Calibri,sans-serif"><b><span lang="FA" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"B Mitra""><span style="color:#0070c0">یافتهها:</span></span></span></span></b><span lang="FA" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"B Mitra""><span style="color:black"> پس از بررسی میزان بیان ژن</span></span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"Times New Roman",serif"><span style="color:black"></span></span></span></span><span lang="FA" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"B Mitra""><span style="color:black">های </span></span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"Times New Roman",serif"><span style="color:black">RXFP1</span></span></span></span><span lang="FA" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"B Mitra""><span style="color:black"> و </span></span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"Times New Roman",serif"><span style="color:black">CTGF</span></span></span></span><span lang="FA" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"B Mitra""><span style="color:black"> بین گروههای کنترل، سالم و کبد چرب، نتایج آزمون آنوا نشان داد که میزان بیان ژنهای </span></span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"Times New Roman",serif"><span style="color:black">RXFP1</span></span></span></span><span lang="FA" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"B Mitra""><span style="color:black"> و </span></span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"Times New Roman",serif"><span style="color:black">CTGF</span></span></span></span><span style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"B Mitra""><span style="color:black"> (به ترتیب 0001/0 </span></span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"Times New Roman",serif"><span style="color:black">p=</span></span></span></span><span lang="FA" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"B Mitra""><span style="color:black"> و 0001/0 </span></span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"Times New Roman",serif"><span style="color:black">p=</span></span></span></span><span lang="FA" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"B Mitra""><span style="color:black">) در گروه کبد چرب، به طور معناداری نسبت به گروه سالم و کنترل افزایش یافته است.</span></span></span></span><span lang="AR-SA" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"B Mitra""><span style="color:black"> در کل نتایج ما نشان داد که با شروع بیماری کبد چرب هردو </span></span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"Times New Roman",serif"><span style="color:black">CTGF</span></span></span></span><span lang="AR-SA" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"B Mitra""><span style="color:black"> و ریلکسین در قلب افزایش یافت و افزایش </span></span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"Times New Roman",serif"><span style="color:black">CTGF</span></span></span></span><span lang="AR-SA" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"B Mitra""><span style="color:black"> نشان از آسیب بافت قلب میباشد لذا این یافتهها میتواند به روشهای درمانی جدید با هدف تعدیل اثرات </span></span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"Times New Roman",serif"><span style="color:black">CTGF</span></span></span></span><span lang="AR-SA" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"B Mitra""><span style="color:black"> و از سویی استفاده از </span></span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"Times New Roman",serif"><span style="color:black">RXFP1</span></span></span></span><span lang="AR-SA" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"B Mitra""><span style="color:black"> به عنوان یک جهت جدید برای مطالعات بالینی بیشتر کمک نماید.</span></span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"Times New Roman",serif"><span style="color:black"></span></span></span></span></span></span></span></span></span></span></span></span><br>
<span style="font-size:11pt"><span style="text-justify:kashida"><span style="text-kashida:0%"><span style="tab-stops:10.5pt"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="line-height:115%"><span style="font-family:Calibri,sans-serif"><b><span lang="FA" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"B Mitra""><span style="color:#0070c0"> نتیجهگیری:</span></span></span></span></b><span lang="FA" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"B Mitra""><span style="color:black"> مدل کبد چرب باعث افزایش بیان </span></span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"Times New Roman",serif"><span style="color:black">CTGF</span></span></span></span><span lang="FA" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"B Mitra""><span style="color:black"> قلبی و از سویی </span></span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"Times New Roman",serif"><span style="color:black">RXFP1</span></span></span></span><span lang="FA" style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"B Mitra""><span style="color:black"> نیز افزایش مییابد.</span></span></span></span></span></span></span></span></span></span></span></span><br>
<span style="font-size:11pt"><span style="text-justify:kashida"><span style="text-kashida:0%"><span style="tab-stops:10.5pt"><span style="line-height:115%"><span style="font-family:Calibri,sans-serif"><b><span style="font-size:10.0pt"><span style="line-height:115%"><span style="font-family:"Times New Roman",serif"><span style="color:#0070c0">Background & Aims:</span></span></span></span></b> <span style="font-size:9.5pt"><span style="line-height:115%"><span style="font-family:"Times New Roman",serif"><span style="color:black">Performing physical activity and having a healthy body is one of the most essential life needs of people with fatty liver. In recent years, studies have been performed on the relationship between fatty liver and arthrosclerosis. The results of these studies indicate the relationship between the Non-alcoholic fatty liver and arthrosclerosis of coronary artery disease. Non-alcoholic fatty liver disease is associated with a sedentary lifestyle and poor eating habits around the world Fatty liver is associated with an increased risk of cardiovascular disease and the formation of atherosclerotic plaques in the carotid arteries and coronary artery stenosis can affect extracellular matrix factors such as CTGF and RXFP1, which play a role in the formation or non-formation of fibrosis. Studies have shown that fatty liver disease can be effective in causing atherosclerotic changes in arteries and increasing the thickness of the carotid artery as an indicator of atherosclerosis, which can be seen even in mild degrees of fatty liver. Relaxin in all parts of the body can have different expressions of RXFP1 receptor in different arteries, so in rats this receptor is strongly expressed in aortic endothelial cells and RXFP1 activates cAMP, cGMP and cAMP signaling pathways in ERK1 / 2 endothelial cells On the other hand CTGF is mainly synthesized by liver cells in the liver and is strongly induced in liver fibrosis CTGF is induced by fibroblast TGF-β cells and mediates the growth and secretion of extracellular matrix. These results indicate that CTGF is the mediator of many TGF-β-probiotic activities</span></span></span></span></span></span></span></span></span></span><br>
<span style="font-size:11pt"><span style="text-justify:kashida"><span style="text-kashida:0%"><span style="tab-stops:10.5pt"><span style="line-height:115%"><span style="font-family:Calibri,sans-serif"><span style="font-size:9.5pt"><span style="line-height:115%"><span style="font-family:"Times New Roman",serif"><span style="color:black">Therefore, the aim is to investigate the effect of this disease on two extracellular matrix genes of the heart.</span></span></span></span></span></span></span></span></span></span><br>
<span style="font-size:11pt"><span style="text-justify:kashida"><span style="text-kashida:0%"><span style="tab-stops:10.5pt"><span style="line-height:115%"><span style="font-family:Calibri,sans-serif"><b><span style="font-size:9.5pt"><span style="line-height:115%"><span style="font-family:"Times New Roman",serif"><span style="color:#0070c0">Methods:</span></span></span></span></b><span style="font-size:9.5pt"><span style="line-height:115%"><span style="font-family:"Times New Roman",serif"><span style="color:black"> In this experimental study, 24 male Wistar rats weighing 200-250 g were randomly divided into 3 groups: control, healthy and fatty liver steatosis. The control group was initially performed in the victim and tissue study And the two healthy and fatty liver groups spent two weeks in the same condition There was a healthy group from the beginning to the end of the study and they did not receive any intervention. Mice in the fatty liver group received oral tetracycline at a dose of 100 mg / kg at a dose of 1.5 ccs per mouse for two weeks. The average weight of the mice was 300 g, of which 100 mg / kg was used for 3 mice, of which 100 mg was dissolved in 4.5 cc and each rat was gavaged 1.5 cc. Fatty liver was modified by measuring liver enzymes (SGPT) and a number of biochemical variables. At the end of the second week, rats two groups were healthy and fatty liver48 hours after the last day (10 to 12 hours of fasting), the studied rats in each group were anesthetized by intraperitoneal injection of a mixture of 10% ketamine at a dose of 50 mg/kg and 2% xylosin at a dose of 10 mg/kg. became were sacrificed and heart tissue sample were taken to test for RXFP1 and CTGF gene expression. In each group, tissue analysis was performed by Real Time PCR technique. First, primer design was performed and then total RNA was extracted from tissues and converted to cDNA. Then cDNA was Replicated by PCR and examined for the expression of the mentioned genes.</span></span></span></span></span></span></span></span></span></span><br>
<span style="font-size:11pt"><span style="text-justify:kashida"><span style="text-kashida:0%"><span style="tab-stops:10.5pt"><span style="line-height:115%"><span style="font-family:Calibri,sans-serif"><b><span style="font-size:9.5pt"><span style="line-height:115%"><span style="font-family:"Times New Roman",serif"><span style="color:#0070c0">Results:</span></span></span></span></b> <span style="font-size:9.5pt"><span style="line-height:115%"><span style="font-family:"Times New Roman",serif"><span style="color:black">After the second week and examining expression level of RXFP1 and CTGF genes between control, healthy and fatty liver groups, ANOVA test results showed that the expression level ofRXFP1 and CTGF genes (p = 0.0001 and p = 0.0001, respectively) In the fatty liver group, significantly increased compared to the healthy and control groups Considering the value of P<0.05, the null hypothesis that there is no significant difference between the level of RXFP1 in different research groups was rejected with 95% confidence. The results between the steatosis group and the other two groups were significant in increasing the level of RXFP1 gene expression. Therefore, it can be said that in the presence of fatty liver, the expression of RXFP1 gene increases in the heart tissue of male rats in order to inhibit fibrosis. Also, in terms of significance, the results between the steatosis group and the other two groups were significant in increasing the level of CTGF gene expression. Therefore, it can be said that in the presence of fatty liver in the steatosis model, the CTGF gene expression increases in line with the increase in cardiac fibrosis.</span></span></span></span></span></span></span></span></span></span><br>
<span style="font-size:11pt"><span style="text-justify:kashida"><span style="text-kashida:0%"><span style="tab-stops:10.5pt"><span style="line-height:115%"><span style="font-family:Calibri,sans-serif"><span style="font-size:9.5pt"><span style="line-height:115%"><span style="font-family:"Times New Roman",serif"><span style="color:black">Overall, our results showed that with the onset of fatty liver disease, both connective tissue growth factors and relaxin increased in the heart, and an increase in connective tissue growth factor indicates cardiac tissue damage, which can lead to heart tissue fibrosis. Therefore, these findings can help new therapies aimed at modulating the effects of CTGF and the use of RXFP1 as a new direction for further clinical studies. Our other findings showed that with induction of fatty liver, the level of RXFP1 in heart tissue increased from the beginning and did not change until the end of the two weeks. The expression level of RXFP1 gene in steatosis fatty liver groups (BS, CS) was significantly higher than the other 2 groups on the other hand the increase in connective tissue growth factor (CTGF) in this study was probably to produce extracellular matrix and compensate for their degradation, and the increase in RXFP1 was to prevent collagen deposition in ECM connective tissue growth factor (CTGF) in cardiac tissue increased sharply, such that its rate increased up to 7 times in the first two weeks compared to the control group, and this increase continued until the end of the two weeks, that increased 10 times However, this method should be considered with more caution because high expression of CTGF increases the level of fibronectin, collagen I and III proteins in the extracellular matrix, followed by myocardial infarction</span></span></span></span></span></span></span></span></span></span><br>
<span style="font-size:11pt"><span style="text-justify:kashida"><span style="text-kashida:0%"><span style="tab-stops:10.5pt"><span style="line-height:115%"><span style="font-family:Calibri,sans-serif"><b><span style="font-size:9.5pt"><span style="line-height:115%"><span style="font-family:"Times New Roman",serif"><span style="color:#0070c0">Conclusion:</span></span></span></span></b><span style="font-size:9.5pt"><span style="line-height:115%"><span style="font-family:"Times New Roman",serif"><span style="color:black"> The fatty liver model of steatosis increases the expression of cardiac CTGF gene and fibrosis, and also increases the RXFP1 gene, which has anti-fibrosis activity. CTGF (CCN2) in response to tissue damage initiates signaling pathways of connective tissue regeneration Therefore, and cardiac tissue fibrosis. RXFP1, which is a component of the extracellular matrix and is most commonly expressed in aortic endothelial cells exerts most of its physiological effect on the cardiovascular system through NO (Nitric oxide).</span></span></span></span></span></span></span></span></span></span>
کبد چرب. ژنهای RXFP1 و CTGF
Fatty liver,RXFP1,CTGF genes
1
11
http://rjms.iums.ac.ir/browse.php?a_code=A-10-6161-1&slc_lang=fa&sid=1
Masoud
Hamzehlo
مسعود
حمزه لو
3900319475328460069579
3900319475328460069579
No
PhD Student of Exercise Physiology Department of Physical Education, Borujerd Branch, Islamic Azad University, Borujerd, Iran
دانشجوی دکتری فیزیولوژی ورزشی، گروه تربیت بدنی، واحد بروجرد، دانشگاه آزاد اسلامی بروجرد، ایران
Mania
Roozbayani
مانیا
روزبیانی
m.roozbayani@iaub.ac.ir
3900319475328460069580
3900319475328460069580
Yes
Assistant Professor of Exercise Physiology Department of Physical Education, Borujerd Branch, Islamic Azad University, Borujerd, Iran
استادیار فیزیولوژی ورزش، گروه تربیت بدنی، واحد بروجرد، دانشگاه آزاد اسلامی، بروجرد، ایران
Hossin
Shirvani
حسین
شیروانی
3900319475328460069581
3900319475328460069581
No
Associate Professor of Sports Physiology, Sports Physiology Research Center, Life style Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
دانشیار فیزیولوژی ورزش، مرکز تحقیقات فیزیولوژی ورزشی، پژوهشکده سبک زندگی، دانشگاه علوم پزشکی بقیه الله (عج)، تهران، ایران