تأثیر تمرینات هوازی و مصرف ویتامین B6 و امگا3 بر بیان ژن‌های وابسته به اتوفاژی ناشی از اندومتریوز در موش‌های ماده

نوع مقاله : مقاله پژوهشی

نویسندگان

گروه فیزیولوژی ورزشی، واحد ساری، دانشگاه آزاد اسلامی، ساری، ایران

چکیده

زمینه و هدف: اندومتریوز یک بیماری التهابی وابسته به استروژن است که 5-10 درصد زنان را در سن باروری تحت تأثیر قرار می‌دهد. در پاتوژنز بیماری اندومتریوز مسیرهای سلولی گوناگونی درگیرند. یکی از این مسیرها اتوفاژی است. اتوفاژی یک فرایند برنامه‌ریزی‌شده از نظر ژنتیکی و تکاملی حفاظت‌شده است که پروتئین‌های سلولی با عمر طولانی و ارگانل‌ها را تخریب می‌کند. هدف از پژوهش حاضر بررسی تأثیر تمرینات هوازی و مصرف ویتامین B6 و امگا3 بر بیان ژن‌های مرتبط با اتوفاژی ناشی از اندومتریوز در موش‌های ماده بود.
 مواد و روش‌ها: در این پژوهش تجربی، از 40 سر موش صحرایی نر بالغ نژاد ویستار با سن حدود هشت هفته استفاده شد. موش‌ها پس از انتقال به محیط آزمایشگاه و پس از دو هفته آشنایی با محیط جدید و ایجاد اندومتریوز، به‌صورت تصادفی و به تعداد مساوی پنج سر موش در هر گروه، به گروه‌های کنترل-سالم، اندومتریوز، شم، اندومتریوز+تمرین، اندومتریوز+B6، اندومتریوز+امگا3، اندومتریوز+تمرین+B6، اندومتریوز+تمرین+ امگا3 جایگزین شدند. مدت زمان تمرین در آب، روزانه ۳۰ دقیقه تا پایان مدت تمرین بود. دو هفته پس از ایجاد مدل اندومتریوز، مکمل امگا3 با دوز 2 میلی‌لیتر در کیلوگرم به گروه‌های اندومتریوز+امگا3 و اندومتریوز+تمرین+ امگا3 و مکمل ویتامین B6 به میزان kg/mg 60 وزن بدن موش‌های صحرایی به گروه‌های آندومتریوز+B6 و آندومتریوز+تمرین+B6 به‌صورت روزانه و به شکل گاواژ خورانده شد. به‌منظور تجزیه‌وتحلیل داده‌ها از تحلیل واریانس یکطرفه استفاده شد.
نتایج: نتایج نشان داد میزان بیان ژن‌های LC3-1 و LC3-II در گروه اندومتریوز نسبت به گروه کنترل-سالم به‌طور معناداری بیشتر بود (0001/0>P) و مقادیر بیان ژن‌هایLC3-1  و LC3-II گروه‌های اندومتریوز+تمرین، اندومتریوز+امگا3، آندومتریوز+B6، آندومتریوز+تمرین +B6 و اندومتریوز+تمرین+امگا3 نسبت به گروه اندومتریوز به‌طور معناداری کمتر بود (0001/0>P). مقادیر آن‌ها در گروه اندومتریوز+تمرین+ B6و اندومتریوز+تمرین+امگا3 نسبت به گروه‌های دیگر به‌طور معنادار کمتر بود (0001/0>P). همچنین نتایج نشان داد میزان بیان ژن‌های FOXO3  و LC3-II/I در گروه اندومتریوز نسبت به گروه کنترل-سالم به‌طور معناداری کمتر بود (0001/0>P). میزان بیان ژن‌های FOXO3 و I LC3-II/ گروه‌های اندومتریوز+تمرین، اندومتریوز+امگا3، آندومتریوز+B6، آندومتریوز+تمرین +B6 و اندومتریوز+تمرین+امگا3 نسبت به گروه اندومتریوز به‌طور معناداری بیشتر بود (05/0>P). مقادیر آن‌ها در گروه اندومتریوز+تمرین+ B6و اندومتریوز+تمرین+ امگا3 نیز نسبت به گروه‌های دیگر به‌طور معناداری بیشتر بود (0001/0>P).
نتیجه‌گیری: به‌طور کلی نتایج پژوهش حاضر بیانگر آن است که افزایش بیان ژن‌های اتوفاژی که در اندومتریوز ایجاد شده، می‌تواند با فعالیت ورزشی منظم هوازی مانند شنا و مکمل امگا3 و B6 مهار شود. شاید اختلال آسیب‌شناختی ایجادشده در اتوفاژی با انجام فعالیت ورزشی و مکمل امگا3 و B6 از طریق کاهش تنظیمی بیان ژن‌های LC3-I ، LC3-II و افزایش بیان ژن‌های FOXO و نسبت LC3-I  / LC3-II  در بهبود اندومتریوز کمک‌کننده باشد.

کلیدواژه‌ها

موضوعات


عنوان مقاله [English]

The effect of aerobic exercise and consumption of vitamin B6 and omega-3 on the expression of genes related to autophagy caused by endometriosis in female rats

نویسندگان [English]

  • Zahra Rezaie
  • Parvin Farzanegi
  • Hajar Abbaszadeh
Exercise Physiology Department, Sari Branch, Islamic Azad University, Sari, Iran
چکیده [English]

Background and Purpose: Endometriosis is an estrogen-dependent inflammatory disease that affects 5-10% of women of reproductive age. Different cellular pathways are involved in the pathogenesis of endometriosis. One of these pathways is autophagy. Autophagy is a genetically and evolutionarily conserved programmed process that degrades long-lived cellular proteins and organelles. The aim of this study was to investigate the effect of aerobic exercise and consumption of vitamin B6 and omega-3 on the expression of genes related to autophagy caused by endometriosis in female rats.
Materials and Methods: In this experimental study, 40 adult male Wistar rats were about eight weeks old. After transferring the rats to the laboratory environment and after two weeks of familiarization with the new environment and creating the endometriosis model, randomly and with an equal number of five rat in each group, they were divided into the control-healthy, endometriosis, sham, endometriosis+exercise, endometriosis+B6, endometriosis+omega-3, endometriosis+exercise groups after creating an endometriosis model+ B6, endometriosis+exercise+omega-3 were categorized. The duration of training in the water was 30 minutes daily until the end of the training period. Two weeks after the creation of the model, omega-3 supplement at a dose of 2 ml/kg to the endometriosis+omega-3 and endometriosis+exercise+omega-3 groups and vitamin B6 supplement at the rate of 60 kg/mg body weight of the rats to the groups endometriosis+B6 and endometriosis+exercise+B6 were taken daily in the form of gavage. One-way analysis of variance was used to analyze the data.
Results: The results showed that the expression levels of LC3-1 and LC3-II genes in the endometriosis group were significantly higher than the healthy control group (P<0.0001) and the expression levels of LC3-1 and LC3-II genes in the group endometriosis+exercise, endometriosis+omega-3, endometriosis+B6, endometriosis+exercise+B6 and endometriosis+exercise+omega-3 were significantly lower than the endometriosis group (P<0.0001). Their values in endometriosis+exercise+B6 and endometriosis+exercise+omega-3 groups were significantly lower than other groups (P<0.0001). Also, the results showed that the expression levels of FOXO3 and LC3-II/I genes in the endometriosis group were significantly lower than in the healthy control group (p<0.0001). The expression levels of FOXO3 and LC3-II/I genes in endometriosis+exercise, endometriosis+omega-3, endometriosis+B6, endometriosis+exercise+B6 and endometriosis+exercise+omega-3 groups were significantly higher than the endometriosis group (P<0.05). Their values in endometriosis+exercise+B6 and endometriosis+exercise+omega-3 groups were significantly higher than other groups (P<0.0001).
Conclusion: In general, the results of the present research indicate that the increased expression of autophagy genes that occurs in endometriosis can be inhibited by regular aerobic exercise such as swimming and omega-3 and B6 supplements. Probably, the pathological disorder caused in autophagy by exercising and supplementing omega-3 and B6 through the regulatory reduction of the expression of lc3-I, lc3-II genes and the increase of the expression of FOXO3 genes and the ratio of lc3-II / lc3-I helps in improving endometriosis.

کلیدواژه‌ها [English]

  • Autophagy
  • Endometriosis
  • Aerobic exercise
  • Omega-3
  • B6
  1. Colette S, Donnez J. "Are aromatase inhibitors effective in endometriosis treatment?". Expert Opinion on Investigational Drugs. 2011; 20 (7): 917–31.
  1. Fang J, Piessens S. "A step‐by‐step guide to sonographic evaluation of deep infiltrating endometriosis". Sonography. 2018; 5 (2): 67–75
  2. Hippert MM, O'Toole PS, Thorburn A. Autophagy in cancer: good, bad, or both?. Cancer research. 2006; 66(19):9349-51
  3. Adraskela K, Veisaki E, Koutsilieris M, Philippou A. Physical exercise positively influences breast cancer evolution. Clinical breast cancer. 2017; 17(6):408-17.
  4. Ardery S, Horn A, Opoku‐Acheampong A, Baumfalk D, Behnke B. Exercise training does not alter prostate tumor cell growth in rat serum or prostate conditioned media . The FASEB Journal. 2018; 32:855-19.
  5. Almeida PW, Gomes-Filho A, Ferreira AJ, Rodrigues CE, Dias-Peixoto MF, Russo RC, et al. Swim training suppresses tumor growth in mice. Journal of applied physiology. 2009; 107(1):261-5.
  6. He JH, Luo RZ, Cai MY, Li M, Lu JB, Yuan ZY. Decreased expression of light chain 3 (LC3) increased the risk of distant metastasis in triple-negative breast cancer. Medical Oncology. 2013; 30(1):468.
  7. Chen CY, Hsu HC, Lee BC, Lin HJ, Chen YH, Huang HC, et al. Exercise training improves cardiac function in infarcted rabbits: involvement of autophagic function and fatty acid utilization. European journal of heart failure. 2010; 12(4):323-30.
  8. Jokar M, Sherafati Moghadam M. High intencity interval training inhibits autophagy in the heart tissue of type 2 diabetic rats by decreasing the content of FOXO3A and BECLIN-1 protents. Iranian Journal of Diabetes and Metabolism. 2019; 18(6): 292-9.
  9. Agha-Alinejad H, Hashemi Jokar E. Effect of Six Weeks of Interval Exercise Training along with Selenium Nanoparticle Ingestion on Bcl-2 and LC3 Genes expression in the Tumor Tissue of Breast Tumor–Bearing Mice. Iranian Quarterly Journal of Breast Disease. 2019; 12(2):26-37.
  10. Montenegro ML, Bonocher CM, Meola J, Portella RL, Ribeiro-Silva A, Brunaldi MO, et al. Effect of Physical Exercise on Endometriosis Experimentally Induced in Rats. Reproductive Sciences. 2019; 26(6):785-793.
  11. Abokhrais IM, Denison FC, Whitaker LH, Saunders PT, Doust A, Williams LJ, et al. A two-arm parallel double-blind randomised controlled pilot trial of the efficacy of Omega-3 polyunsaturated fatty acids for the treatment of women with endometriosis-associated pain (PurFECT1). Plos one. 2020; 15(1):e0227695.
  12. Mohammadikhou T, Ebrahim K, Nikbakht H. The Effect of 12 Weeks of Training with Omega Supplement on Serum Levels of Chemerin and Insulin Resistance in Obese Inactive Women. Sport Physiology & Management Investigations. 2015; 7(3):49-58. (In Persian).
  13. Zekri Kondalaji R, Sarisarraf V, Nourshahi M. Investigating the effect of 4-week fish oil supplementation on inflammation and plasma nitric oxide and reactive oxygen species in response to exhaustive exercise. Journal of Sport and Exercise Physiology. 2020; 13(1):16-26. (In Persian).
  14. Spinner MA, Sanchez LA, Hsu AP, Shaw PA, Zerbe CS, Calvo KR, et al. GATA2 deficiency: a protean disorder of hematopoiesis, lymphatics, and immunity. Blood, The Journal of the American Society of Hematology. 2014; 123(6):809-21.
  15. Shimizu R, Yamamoto M "GATA-related hematologic disorders". Experimental Hematology. 2016; 44(8): 696–705.
  16. Ruoss C, Tadros A, O’Shea T, McFarlane J, Almahbobi G. Ovarian follicle development in Booroola sheep exhibiting impaired bone morphogenetic protein signalling pathway. J Reprod. 2009; 138(4): 689-96.
  17. Kiani K, Movahedin M, Malekafzali H, Mirfasihi F, Nargess Sadati S.N, Moini A, et al. Effect of the estrus cycle stage on the establishment of murine endometriosis lesions. Int J Reprod Biomed (Yazd). 2018; 16(5): 305–314.
  18. Manna I, Jana K, Samanta PK. Effect of intensive exercise-induced testicular gametogenic and steroidogenic disorders in mature male Wistar strain rats: a correlative approach to oxidative stress. Acta Physiol Scand. 2003; 178:33–40.
  19. Ghule AE, Kandhare AD, Jadhav SS, Zanwar AA, Bodhankar SL. Omega-3-fatty acid adds to the protective effect of flax lignan concentrate in pressure overload-induced myocardial hypertrophy in rats via modulation of oxidative stress and apoptosis. International Immunopharmacology. 2015; 28(1):751-63.
  1. Rasha H. M. The Impact of Vitamin B 6 Supplementation on Experimental Colitis and Colonic Mucosal DNA Content in Female Rats Fed High Sucrose Diet. Australian Journal of Basic and Applied Sciences. 2011; 5(5): 1051-1060.
  1. Tran TA, Ahn KS, Song YW, Moon JY, Cho M, Lim Y, et al. Mechanism of 2′, 3′-dimethoxyflavanone-induced apoptosis in breast cancer stem cells: Role of ubiquitination of caspase-8 and LC3. Archives of biochemistry and biophysics. 2014; 562:92-102.
  2. Shamsi MM, Chekachak S, Soudi S, Gharakhanlou R, Quinn LS, Ranjbar K, et al. Effects of exercise training and supplementation with selenium nanoparticle on T-helper 1 and 2 and cytokine levels in tumor tissue of mice bearing the 4 T1 mammary carcinoma. Nutrition. 2019; 57:141-7.
  3. Jain A. P62/SQSTM1 is a target gene for transcription factor NRF2 and creates elementdriven gene transcription. J.Biol. Chem. 2010; 285:22576-22591.
  4. Wirawan E, Berghe TV, Lippens S, Agostinis P, Vandenabeele P. Autophagy: for better or for worse. Cell research. 2012; 22(1):43-61.
  1. Scherz-Shouval R, Elazar Z. ROS, mitochondria and the regulation of autophagy. Trends in cell biology. 2007; 17(9):422-7.
  1. Lee Y, Kwon I, Jang Y, Song W, Cosio-Lima LM, Roltsch MH. Potential signaling pathways of acute endurance exercise-induced cardiac autophagy and mitophagy and its possible role in cardioprotection. The Journal of Physiological Sciences. 2017; 67(6):639-54.
  1. Siomara Hernandez, Myrella L. Cruz, Annelyn Torres-Reveron, Caroline B. Appleyard. Impact of physical activity on pain perception in an animal model of endometriosis. J Endometr Pelvic Pain Disord. 2015; 7(3): 89–114.
  1. Brandt N, Gunnarsson TP, Bangsbo J, Pilegaard H. Exercise and exercise training‐induced increase in autophagy markers in human skeletal muscle. Physiological reports. 2018; 6(7):e13651.
  2. Zhuang J, Kamp WM, Li J, Liu C, Kang JG, Wang PY, et al. Forkhead box O3A (FOXO3) and the mitochondrial disulfide relay carrier (CHCHD4) regulate p53 protein nuclear activity in response to exercise. Journal of Biological Chemistry. 2016; 291(48):24819-27.
  3. Bertaggia E, Coletto L, Sandri M. Posttranslational modifications control FOXO3 activity during denervation. American Journal of Physiology-Cell Physiology. 2012; 302(3):C587-96.
  4. Lundell LS, Massart J, Altıntaş A, Krook A, Zierath JR. Regulation of glucose uptake and inflammation markers by FOXO1 and FOXO3 in skeletal muscle. Molecular metabolism. 2019; 20:79-88
  5. Stefanetti RJ, Lamon S, Wallace M, Vendelbo MH, Russell AP, Vissing K. Regulation of ubiquitin proteasome pathway molecular markers in response to endurance and resistance exercise and training. Pflügers Archiv-European Journal of Physiology. 2015; 467(7):1523-37.
  6. Krupa A, Padała O, Putowski M, Konopelko M, Piasek E. Available treatment methods for endometriosis. Journal of Education, Health and Sport. 2019; 9(7):178-84.
  7. Wakefield SL, Lane M, Schulz SJ, Hebart ML, Thompson JG, Mitchell M. Maternal supply of omega-3 polyunsaturated fatty acids alter mechanisms involved in oocyte and early embryo development in the mouse. American Journal of Physiology-Endocrinology and Metabolism. 2008; 294(2):E425-34.
  8. Arem H, Neuhouser ML, Irwin ML, Cartmel B, Lu L, Risch H, et al. Omega-3 and omega-6 fatty acid intakes and endometrial cancer risk in a population-based case–control study. European journal of nutrition. 2013; 52(3):1251-60.
  9. Hansen SO, Knudsen UB. Endometriosis, dysmenorrhoea and diet. European Journal of Obstetrics & Gynecology and Reproductive Biology. 2013; 169(2):162-71.
  10. Ciavattini A, Serri M, Carpini GD, Morini s, Clemente N. Ovarian endometriosis and vitamin D serum levels. Gynecological Endocrinology. 2017; 33(2):164-7.
  11. Ghasemian Langharodi S, Farzanegi P, Moradi L. The Effect of Swimming Training and Vitamin B6 Intake on ALDH1A2 gene Expression in Endometriosis Rat. Razi J of Medical Sciences. 2021; 28(3):152-162.
  • تاریخ دریافت: 19 آبان 1401
  • تاریخ بازنگری: 15 بهمن 1401
  • تاریخ پذیرش: 26 بهمن 1402
  • تاریخ اولین انتشار: 26 بهمن 1402
  • تاریخ انتشار: 01 تیر 1402