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
1399
7
1
gregorian
2020
10
1
27
7
online
1
fulltext
fa
تاثیر شش هفته تمرین تداومی و تناوبی شدید بر بیان ژن عامل رشد بتا، ماتریکس متالوپروتیناز-2 و مهارکننده بافتی متالوپروتیناز-1 بافت ریه در رتهای نر ویستار
Effects of 6-weeks of continuous and HIIT training on gene expression of TGF-B, MMP-2 and TIMP-1 in lung tissues of male wistar rats
فیزیولوژی ورزش
Exercise Physiology
پژوهشي
Research
<strong><span style="color:#0070c0;"><span style="font-family:B Mitra;"><span style="font-size:10.0pt;">زمینه و هدف: </span></span></span></strong><span style="color:black;"><span style="font-family:B Mitra;"><span style="font-size:10.0pt;">مطالعات نشان می دهد که داروهای ضد التهاب درمان موثری برای فیبروز و التهاب ریوی نبوده است. </span></span></span><span style="color:black;"><span style="font-family:B Mitra;"><span style="font-size:10.0pt;">هدف از این تحقیق بررسی تاثیر شش هفته تمرینات تداومی و تناوبی شدید بر بیان ژن عامل رشد بتا، ماتریکس متالوپروتیناز-2 و مهارکننده بافتی متالوپروتیناز-1 بافت ریه در رت­های نر ویستار بود. </span></span></span><br>
<strong><span style="color:#0070c0;"><span style="font-family:B Mitra;"><span style="font-size:10.0pt;">روش</span></span></span></strong><strong><span dir="LTR"><span style="color:#0070c0;"><span style="font-family:Times New Roman,serif;"><span style="font-size:10.0pt;">­</span></span></span></span></strong><strong><span style="color:#0070c0;"><span style="font-family:B Mitra;"><span style="font-size:10.0pt;"> کار:</span></span></span></strong> <span style="color:black;"><span style="font-family:B Mitra;"><span style="font-size:10.0pt;">در این مطالعه ­تجربی، 18 سر رت نر ویستار </span></span></span><span style="color:black;"><span style="font-family:B Mitra;"><span style="font-size:10.0pt;">(6 تا 8 ماهه) انتخاب و به­طور تصادفی در سه گروه کنترل (</span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:Times New Roman,serif;"><span style="font-size:10.0pt;">Con</span></span></span></span><span style="color:black;"><span style="font-family:B Mitra;"><span style="font-size:10.0pt;">)، تمرین تداومی شدت متوسط (</span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:Times New Roman,serif;"><span style="font-size:10.0pt;">MICT</span></span></span></span><span style="color:black;"><span style="font-family:B Mitra;"><span style="font-size:10.0pt;">) و تمرین تناوبی شدید (</span></span></span><a name="_Hlk16406947"><span dir="LTR"><span style="color:black;"><span style="font-family:Times New Roman,serif;"><span style="font-size:10.0pt;">HIIT</span></span></span></span></a><span style="color:black;"><span style="font-family:B Mitra;"><span style="font-size:10.0pt;">) قرار گرفتند. برنامه تمرین تداومی شامل 15 تا30 دقیقه دویدن روی تردمیل با شدت 65-70 درصد </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:Times New Roman,serif;"><span style="font-size:10.0pt;">VO<sub>2</sub>max</span></span></span></span><span style="color:black;"><span style="font-family:B Mitra;"><span style="font-size:10.0pt;">، پنج روز در هفته به مدت 6هفته بود. برنامه تمرین تناوبی شدید نیز شامل 5 تا 8 تناوب (2 دقیقه­ای) با شدت 80 تا 100درصد </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:Times New Roman,serif;"><span style="font-size:10.0pt;">VO<sub>2</sub>max</span></span></span></span><span style="color:black;"><span style="font-family:B Mitra;"><span style="font-size:10.0pt;"> و 2 دقیقه ریکاوری با شدت 50 تا 60 درصد </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:Times New Roman,serif;"><span style="font-size:10.0pt;">VO<sub>2</sub>max</span></span></span></span><span style="color:black;"><span style="font-family:B Mitra;"><span style="font-size:10.0pt;"> بین هر تناوب) به مدت 6هفته بود.</span></span></span><span style="color:black;"><span style="font-family:B Mitra;"><span style="font-size:10.0pt;"> بیان ژن</span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:Times New Roman,serif;"><span style="font-size:10.0pt;">TGF-β </span></span></span></span><span style="color:black;"><span style="font-family:B Mitra;"><span style="font-size:10.0pt;">، </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:Times New Roman,serif;"><span style="font-size:10.0pt;">MMP-2</span></span></span></span><span style="color:black;"><span style="font-family:B Mitra;"><span style="font-size:10.0pt;"> و</span></span></span> <span dir="LTR"><span style="color:black;"><span style="font-family:Times New Roman,serif;"><span style="font-size:10.0pt;">TIMP-1</span></span></span></span> <span style="color:black;"><span style="font-family:B Mitra;"><span style="font-size:10.0pt;">با روش </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:Times New Roman,serif;"><span style="font-size:10.0pt;">Real Time PCR</span></span></span></span> <span style="color:black;"><span style="font-family:B Mitra;"><span style="font-size:10.0pt;">اندازه­گیری شد.</span></span></span><span style="color:black;"><span style="font-family:B Mitra;"><span style="font-size:10.0pt;"> داده</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 Mitra;"><span style="font-size:10.0pt;">ها به روش تحلیل واریانس یک­طرفه و آزمون تعقیبی </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:Times New Roman,serif;"><span style="font-size:10.0pt;">LSD</span></span></span></span><span style="color:black;"><span style="font-family:B Mitra;"><span style="font-size:10.0pt;"> در سطح معنی­داری 05/0 </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<</span></span></span></span><span style="color:black;"><span style="font-family:B Mitra;"><span style="font-size:10.0pt;"> تجزیه و تحلیل شدند.</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:#0070c0;"><span style="font-family:B Mitra;"><span style="font-size:10.0pt;">یافته­ها:</span></span></span></strong> <span style="color:black;"><span style="font-family:B Mitra;"><span style="font-size:10.0pt;">تمرینات تداومی و تناوبی شدید به کاهش معنی­دار بیان ژن </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:Times New Roman,serif;"><span style="font-size:10.0pt;">MMP-2</span></span></span></span><span style="color:black;"><span style="font-family:B Mitra;"><span style="font-size:10.0pt;"> و افزایش معنی­دار بیان ژن </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:Times New Roman,serif;"><span style="font-size:10.0pt;">TIMP-1</span></span></span></span><span style="color:black;"><span style="font-family:B Mitra;"><span style="font-size:10.0pt;"> و </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:Times New Roman,serif;"><span style="font-size:10.0pt;">TGF-β</span></span></span></span><span style="color:black;"><span style="font-family:B Mitra;"><span style="font-size:10.0pt;"> بافت ریه نسبت به گروه کنترل منجر شدند (001/0</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=</span></span></span></span><span style="color:black;"><span style="font-family:B Mitra;"><span style="font-size:10.0pt;">). تفاوت معنی­داری در بیان نسبی </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:Times New Roman,serif;"><span style="font-size:10.0pt;">MMP-2</span></span></span></span><span style="color:black;"><span style="font-family:B Mitra;"><span style="font-size:10.0pt;"> بین دو گروه </span></span></span><span style="color:black;"><span style="font-family:B Mitra;"><span style="font-size:10.0pt;">تمرین </span></span></span><span style="color:black;"><span style="font-family:B Mitra;"><span style="font-size:10.0pt;">تداومی و </span></span></span><span style="color:black;"><span style="font-family:B Mitra;"><span style="font-size:10.0pt;">تمرین </span></span></span><span style="color:black;"><span style="font-family:B Mitra;"><span style="font-size:10.0pt;">تناوبی شدید مشاهده نشد<a name="_Hlk16235563"></a><a name="_Hlk17094230"> (832/0</a></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=</span></span></span></span><span style="color:black;"><span style="font-family:B Mitra;"><span style="font-size:10.0pt;">)، اما بیان ژن</span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:Times New Roman,serif;"><span style="font-size:10.0pt;">TIMP-1 </span></span></span></span><span style="color:black;"><span style="font-family:B Mitra;"><span style="font-size:10.0pt;"> و </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:Times New Roman,serif;"><span style="font-size:10.0pt;">TGF-β</span></span></span></span><span style="color:black;"><span style="font-family:B Mitra;"><span style="font-size:10.0pt;"> در گروه تمرین تناوبی شدید نسبت به گروه تمرین تداومی به میزان معنی­داری بالاتر بود</span></span></span><span style="color:black;"><span style="font-family:B Mitra;"><span style="font-size:10.0pt;"> (001/0</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=</span></span></span></span><span style="color:black;"><span style="font-family:B Mitra;"><span style="font-size:10.0pt;">).</span></span></span><br>
<strong><span dir="RTL"><span style="color:#0070c0;"><span style="font-family:B Mitra;"><span style="font-size:10.0pt;">نتیجه­گیری:</span></span></span></span></strong> <span dir="RTL"><span style="color:black;"><span style="font-family:B Mitra;"><span style="font-size:10.0pt;">به­نظر می­رسد، تمرین تناوبی شدید احتمالاً می­تواند مداخله موثرتری برای کاهش فیبروز و التهاب بافت ریه باشد.</span></span></span></span>
<strong>Background:</strong> In pathological studies, there is usually a low degree of Pulmonary inflammation, and due to the presence of inflammatory cells in the lung tissue, there are discussions about the role of these cells in the progression of the disease (1). Matrix metalloproteinases (MMPs) are super family of proteolytic enzymes that play an important role in the breakdown of extracellular matrix and fibrosis (2, 3). MMP-2 has the potential to degrade wide range of extracellular matrix proteins, including type IV collagen, basement membrane, fibronectin and gelatin (6). Studies show that MMP-2 activity is increased in pulmonary fibrosis (7). The Tissue Inhibitor of MMPs (TIMPs) gene family are physiological inhibitors of MMPs that inhibit the activity of these proteases. TIMP / MMP imbalance is an important factor in the fibrogenic process (9). Also, in pulmonary fibrosis, the activity of MMPs is regulated by several factors, including growth factor, and inflammatory mediators may play an important role in modulating lung tissue damage and extracellular matrix degradation. Transforming Growth Factor β (TGF-β) is a multifunctional cytokine that plays an important role in causing fibrosis in many tissues, including the lungs (10).<br>
Studies show that exercise can help improve the levels of matrix metalloproteinases and their associated inflammatory factors. However, the results of studies in this field are contradictory, so, decrease in expression and serum levels of MMP-2 in rats following voluntary exercise and High-intensity interval training (HIIT) have been reported (12,13). On the other hand, 12 weeks of resistance training has been shown to increase MMP2 levels in rats (14). Also, significant increase (15) and no change (16) in TGF-β1 tissue values after HIIT was reported in rats.<br>
The effect of different training methods on lung tissue has been considered. Therefore, the aim of this study was to investigate the effects of 6-weeks of continuous and HIIT training on gene expression of TGF-B, MMP-2 and TIMP-1 in lung tissues of male wistar rats.<br>
<strong>Methods:</strong> This is a experimental study. 18 male wistar rats (6 to 8 months) were selected and randomly divided into three groups of control (Con), moderate intensity continuous training (MICT) and High-intensity interval training (HIIT) groups. The aerobic training program consisted of 15 to 30 minutes of treadmill running at 65-70% VO2max intensity, 5 days a week for 6 weeks. The HIIT program consisted of 5 to 8 alternations (2 minutes) of 80 to 100 percent VO2max and 2 minutes of recovery with 50 to 60 percent of VO2max between each period for 6 weeks (17). TGF-β, MMP-2 and TIMP-1 gene expression in lung tissue was measured after training using Real Time PCR. Data were analyzed by one-way ANOVA and LSD post hoc test at the P <0.05.<br>
<br>
<strong>Results:</strong> Table 4 shows the mean and standard deviation of research variables in different groups. The results showed that HIIT and MICT led to significant decrease in MMP-2 gene expression and significant increase in TIMP-1 and TGF-β gene expression in lung tissue compared to the control group (P=0.001). There was no significant difference in the relative expression of MMP-2 between the two groups of HIIT and MICT (P=0.832), but TIMP-1 and TGF-β gene expression was significantly higher in the HIIT group compared to the MICT group (P=0.001) (Fig. 1-3).<br>
<strong>Conclusion: </strong>The findings of the present study show that HIIT and MICT significantly decrease MMP-2 gene expression and significantly increase TIMP-1 and TGF-β gene expression in lung tissues of male wistar rats. The findings of this study were consistent with the results of Previous research (12,13, 23, 27-29). Decreased gene expression of MMP-2 in response to training sessions can be attributed to the expression of endogenous protein inhibitors such as TIMP-1, alpha-2 macroglobulin and protease degradation. Also, the reduction of some inflammatory factors that stimulate MMP-2 due to interval training periods can play a role in this reduction (19). Therefore, according to the mechanisms involved in reducing MMP-2 expression and the findings of the present study, reducing MMP-2 in the HIIT and MICT groups compared to the control group can reduce the expression of TIMP-1 and TGF-β genes after exercise. MMPs are highly regulated at the level of gene transcription and translation in the lung, their expression is through a variety of transcription factors (activators and suppressors, including growth factors, hormones, cytokines, cell adhesion molecules, proteins), extracellular matrix and their bioactive components and intracellular signaling agents (GTPases), all of which can directly or indirectly regulate the expression of MMPs (20). Therefore, HIIT and MICT may alter the gene expression levels of the MMP-2 in lung tissue by affecting the above factors. The reason for the increase in TGF-β1 following exercise is not well understood. However, oxidative stress and exercise-induced hypoxia are two possible mechanisms (33). Studies have shown that by increasing the expression of NADPH oxidase and decreasing the expression of antioxidant enzymes, increases the expression of TGF-β1 in tissue (34,35). HITT is associated with hypoxia at the cell, which leads to increased expression of HIF-1α (Hypoxia-induced Factor 1- α). This factor increases in cells in response to hypoxia and mediates several biological functions. There were some limitations in the present study, such as the lack of measurement of other MMPs. According to the results, it seems that HIIT training may be a more effective intervention to reduce lung fibrosis. Therefore, it is recommended to consider High-intensity interval training programs for the health of the respiratory system.<br>
تمرین تداومی, تمرین تناوبی شدید, عامل تغییر رشد بتا, ماتریکس متالوپروتئیناز-2, مهارکننده بافتی متالوپروتئیناز-1, رتهای صحرائی
Moderate-intensity Interval training, High-intensity interval training, Transforming growth Factor beta, Matrix metalloproteinase-2, Tissue inhibitor matrix metalloproteinase 1, Rats
1
11
http://rjms.iums.ac.ir/browse.php?a_code=A-10-4748-1&slc_lang=fa&sid=1
Shadi
Fahham
شادی
فهام
sh.fahham@gmail.com
3900319475328460054249
3900319475328460054249
No
Department of Pardis Alborz, University of Tehran, Tehran, Iran
دانشکده تربیت بدنی پردیس البرز، دانشگاه تهران، تهران، ایران
Rahman
Soori
رحمان
سوری
Soori@ut.ac.ir
3900319475328460054250
3900319475328460054250
Yes
Faculty of Physical Education and Sport Sciences, University of Tehran, Tehran, Iran
دانشگاه تهران، تهران، ایران
Fatemeh
Shab khiz
فاطمه
شب خیز
shabkhiz@ut.ac.ir
3900319475328460054251
3900319475328460054251
No
University of Tehran, Tehran, Iran
دانشگاه تهران، تهران، ایران
Siroos
Choobineh
سیروس
چوبینه
Choobineh@ut.ac.ir
3900319475328460054252
3900319475328460054252
No
University of Tehran, Tehran, Iran
دانشگاه تهران، تهران، ایران