Razi Journal of Medical Sciences

fa پاسخ عوامل نوروالتهابی مغز در رت‌های مبتلا به آنسفالومیلیت خود ایمن تجربی به اثر حفاظتی تمرینات اینتروال و مصرف ویتامین D The Response of Neuro-Inflammatory Factors in Brain Tissue in Rats with Experimental Autoimmune Encephalomyelitis to the Protective Effect of Interval Training and Vitamin D فیزیولوژی ورزش Exercise Physiology پژوهشي Research <div style="text-align: justify;">زمینه و هدف: مولتیپل اسکلروزیس یک بیماری خودایمن با ضایعات ملتهب و دمیلینیه شونده در سیستم عصبی مرکزی میباشد. هدف از این مطالعه بررسی پاسخ عوامل نوروالتهابی مغز در رت های مبتلا به آنسفالومیلیت خود ایمن تجربی به اثر حفاظتی تمرینات اینتروال و مصرف ویتامین D بود. روش کار: در این پژوهش تجربی، 48سر موش ماده نژاد لوئیز 4هفتهای بهطور تصادفی به 8گروه تقسیم شدند. رتها با نخاع خوکچه هندی و ادجوانت کامل ایمونیزه شدند. مدل EAE در انتهای هفته ششم تمرینات القاء شد. رتها به ازای هر کیلوگرم وزن بدن 5میکروگرم ویتامین  D3در 150میکرولیتر روغن کنجد هر دو روز یک بار به مدت 2هفته بهصورت داخل صفاقی دریافت کردند. پروتکل اینتروال شامل۱۰ تکرار ۱ دقیقهای، نسبت کار به استراحت ۱ به ۲ و کل زمان دویدن ۳۰دقیقه بود. شدت تمرین به تدریج از ۲۵ متر در دقیقه به ۷۰متر در دقیقه افزایش یافت. دادهها به روش آنالیز واریانس یکطرفه و آزمون تعقیبی توکی در سطح معنیداری p<0.05 تجزیه و تحلیل شد.  یافته‌ها: نتایج نشان داد که بین گروهها در شاخص NF-KB و TGF-B تفاوت معنیداری وجود نداشت (05/0p>). میانگین تغییرات IL-17 در گروه ویتامین D در مدل EAE افزایش معنیداری نسبت به گروه کنترل سالم ویتامین D داشت (01/0=P). میانگین تغییرات GM-CSF در گروههای اینتروال سالم (018/0=P)، D کنترل سالم (02/0=P)، D اینتروال سالم(001/0=P) و D اینتروالMS  (03/0=P) کاهش معنیداری نسبت به گروه کنترل سالم داشت. نتیجه گیری: تمرینات اینتروال و ویتامین با بهبود عوامل نوروالتهابی مغز در رت های مبتلا به آنسفالومیلیت خود ایمن تجربی همراه نبود.  </div> <div style="text-align: justify;"> Background & Aims: As a complex disease, MS is characterized by neuroinflammation, demyelination, and sequential axonal loss (1). By identifying inflammatory factors in experimental autoimmune encephalomyelitis, Th17 cells producing interleukin-17 (IL-17) were also added to the list of potential factors involved in the pathogenesis of the disease (2). Transforming growth factor beta (TGF-β) is also a potent regulatory cytokine with diverse effects on hematopoietic cells. The main function of TGF-β in the immune system is to maintain tolerance by regulating lymphocyte proliferation, differentiation and survival. Defects in TGF-beta1 expression or signaling in T cells are associated with the onset of several autoimmune diseases (6). The nuclear transcription factor kappa B (NF-κB) plays a major role in inflammatory diseases through the regulation of inflammation and cell survival. NF-κB has been shown to be activated in multiple cell types in the central nervous system of MS patients, including T cells, microglia/macrophages, astrocytes, oligodendrocytes, and neurons (7). It has also been shown that granulocyte and monocyte growth factor (GM-CSF) may play a role in the pathogenesis of multiple sclerosis (8). Finding suitable methods to reduce the complications of neuroinflammation may lead to the selection of new treatment regimens for many neurological diseases and neurological disorders (1). In a study on multiple sclerosis patients, eight weeks of combined endurance and resistance training was associated with a significant reduction of IL-17 in plasma (10). Also, in another study, both continuous strength and endurance training protocols inhibit the production of pro-inflammatory cytokines such as interleukin-17 in the spinal cord of mice suffering from experimental autoimmune encephalomyelitis (11). Studies have shown that sports activity increases GM-CSF levels in healthy people (12, 13). Also, no change and decrease in TGF-β levels have been reported in patients with multiple sclerosis after exercises (11, 14). Vitamin D deficiency is also associated with the development of multiple sclerosis, which is usually an inflammatory demyelinating disease of the central nervous system in adults (15, 16). Vitamin D3 may act as a regulator of prescription factors and reduce the severity of the disease by inhibiting the production of inflammatory cytokines (17). Considering the important role of exercise in health and the prevention and treatment of diseases such as multiple sclerosis, it seems that the study of the effects of exercise and supplements on neuroinflammatory factors of the brain is of great importance, but according to the researcher's studies, the research conducted in this regard is very limited. In recent studies, support has been provided for the use of vitamin D to improve the inflammatory condition in multiple sclerosis patients. On the other hand, the results of studies related to the effect of exercise training on changes in neuroinflammatory factors of brain tissue are contradictory. Therefore, in the current study, the researcher intends to answer the question of what effect does interval training and vitamin D consumption have on brain neuroinflammatory factors in rats suffering from experimental autoimmune encephalomyelitis? Methods: In this experimental study, 48 male Louise 4-week-old female rats were randomly divided into 8 groups. The training intensity was gradually increased from 25 meters per minute to 70 meters per minute. The rats were immunized with the guinea pig's spit and complete adjuvant. The EAE model was induced at the end of the sixth week of exercise. Rats received 5 μg of body weight per kilogram of vitamin D3 in 150 μl of sesame oil every two days once for 2 weeks’ intraperitoneal injection. The interval protocol consisted of 10 repetitions of 1 minute, the ratio of work to rest was 1:2, and the total running time was 30 minutes. Data were analyzed by one-way analysis of variance and Tukey post hoc test at the p <0.05. Results: The results showed that there was no significant difference between the groups in NF-KB and TGF-B (p>0.05). The average changes of IL-17 in the vitamin D group in the EAE model had significant increase compared to the healthy vitamin D control group (P=0.01). The average changes of GM-CSF in healthy interval groups (P=0.018), D healthy control (P=0.02), D healthy interval (P=0.001) and D interval MS (P=0.03) There was significant decrease compared to the healthy control group. Conclusion: The results of this research showed that six weeks of interval training had no significant effect on NF-KB and TGF-B indicators. Also, the mean changes of IL-17 and GM-CSF in the intervention groups (interval exercises and vitamin D) were not significant compared to the control group of the EAE model. Consistent with the findings of our study, in a study on experimental autoimmune encephalomyelitis rats, it was found that there was no significant difference between the average concentrations of pro-inflammatory cytokines in the vitamin D3 group compared to the control group (10). In the present study, the levels of IL-17 in the brain tissue along with the consumption of vitamin D3 in EAE did not show a significant change, there is a possibility that the dose of vitamin D3 in EAE samples was not sufficient. Studies have shown that sports activity increases G-CSF levels in healthy people (12, 13). The production of TGF-β in the spinal cord tissue of C57 mice was not significantly affected by the treatment with four weeks of resistance training (the initial intensity to start the resistance training program was 25% of the animal's body weight, this value increased from 50 to 75% of the animal's weight) (11) which is consistent with the results of our study. Recent studies have also shown that NF-κB regulates the survival of resident cells in inflammatory lesions (25, 26). Stimuli such as pro-inflammatory cytokines tumor necrosis factor (TNF-α) and interleukin-1 (IL-1) can activate NF-κB. These stimuli activate IκB kinases (IKK), which in turn phosphorylate the major inhibitor of NF-κB, IκBα. This phosphorylation step leads to ubiquitination and subsequent degradation by the IκBα proteasome. The NF-κB complex translocates to the nucleus, where it binds to kB enhancers in the regulatory regions of various genes, where it activates transcription (28). Some studies have shown that the action of protein kinase B (Akt) through IKK is necessary for the activation and phosphorylation of NF-κB. Phospho-AKT mediates the phosphorylation of IKKα, which allows it to phosphorylate IκB and thereby allow NFκB to translocate into the nucleus. In addition, AKT can independently phosphorylate NFκB by directly phosphorylating the p65/RelA subunit to activate IKK (29). Maybe the reason for not changing the indicators after the intervention is the training period. It seems that in this regard, the results of Soltani et al showed that patients with multiple sclerosis can improve their immune system function by reducing TGF-β levels by participating in aerobic exercise in water, although with a long training period more than eight weeks) to profit (14). Therefore, it is possible to achieve clearer results by lengthening the training period. Recent intervention studies show that, unlike continuous moderate exercise, interval exercise reduces inflammatory activity indicators and helps to improve the immune system and is related to disability status, symptoms and disease activity (35). In summary, the research results show that interval training and vitamin D are not associated with the improvement of brain neuroinflammatory factors in rats suffering from experimental autoimmune encephalomyelitis.</div> مولتیپل اسکلروزیس, تمرین اینتروال, ویتامین D, عوامل نوروالتهابی Multiple sclerosis, Interval training, Vitamin D, Neuroinflammatory factors 1 11 http://rjms.iums.ac.ir/browse.php?a_code=A-10-7165-1&slc_lang=fa&sid=1 Smatalsadat Mousavi عصمت السادات موسوی 3900319475328460091181 0009-0004-8452-2742 No PhD Farhangian University, Nasibah Campus, Tehran, Iran دکتری فیزیولوژی ورزشی، دانشگاه فرهنگیان، پردیس نسیبه، تهران، ایران Zia Falahmohammadi ضیاء فلاح محمدی mousavi2753@gmail.com 3900319475328460091182 3900319475328460091182 Yes Associate Professor Department of Exercise Physiology, Faculty of Sport Sciences, University of Mazandaran, Babolsar, Mazandaran, Iran دانشیار، گروه فیزیولوژی ورزش، دانشکده علوم ورزشی، دانشگاه مازندران، بابلسر، ایران