بررسی سطح سرمی آیریزین و بیان ژن و پروتئین فاکتور رشد اندوتلیال عروقی در بافت قلب موش های نژاد nmri به دنبال تمرین مقاومتی و تزریق آیریزین

اهداف: آنژیوژنزیز در عملکرد قلب نقش حیاتی ایفا می کند. آیریزین یک میانجی احتمالی برای اثرات ورزش می باشد. هدف از مطالعه ی حاضر، بررسی سطح سرمی آیریزین و بیان ژن و پروتئین فاکتور رشد اندوتلیال عروقی در بافت قلب موش های نژاد nmri به دنبال تمرین مقاومتی و تزریق آیریزین بود.مواد و روش ها: 21 عدد موش (nmri، پنج هفته ای با وزن حدود 2±18 گرم) به صورت تصادفی به سه گروه کنترل، تمرین (مقاومتی) و آیریزین تقسیم شدند. پروتکل تمرین به مدت هشت هفته‌ اجرا شد. وزنه ای معادل 30 درصد وزن موش ها به دم آن ها متصل و روی یک نردبان با ارتفاع یک متر بالا رفتند. وزنه به تدریج به دو برابر وزن موش می رسید. گروه آیریزین به مدت هشت هفته آیریزین با دوز 100 میکروگرم/کیلوگرم/هفته به صورت داخل صفاقی دریافت کردند. بیان ژن vegfدر قلب با روش real-time pcr، پروتئین vegf با ایمونوهیستوشیمی و وسترن بلات و غلظت سرمی آیریزین با استفاده از الایزا بررسی شد. یافته ها: در مقایسه با گروه کنترل، سایر گروه های مورد مطالعه افزایش بیان ژن و پروتئین vegf و همچنین افزایش سطوح سرمی آیریزین را نشان دادند .(p < 0.05) ضریب همبستگی پیرسون نشان داد که بین پارامترهای مورد نظر در هر گروه رابطه ی معنی‌دار مثبتی وجود دارد(p < 0.05 , r > 0 ) .نتیجه‌گیری: احتمالا آیریزین واسطه ی برقراری ارتباط بین تمرین مقاومتی و آنژیوژنزیز در بافت قلب می باشد.

investigating the serum irisin level and expression of vascular endothelial growth factor gene and protein in the heart tissue of nmri mice after resistance training and irisin injection

extended abstract background and purpose cardiovascular diseases remain the leading cause of death globally, accounting for 31.5% of all deaths (1). while advances in medical science have reduced the mortality rate from heart diseases comparedto the past, major risk factors, such as physical inactivity, continue to play a crucial role in theirprevalence (2) exercise has a positive effect on long-term cardiovascular health. specifically, regularphysical activity plays a key role in reducing vascular resistance and stiffness (2). by inducingbeneficial adaptations like angiogenesis, exercise enhances heart function, lowers the risk ofcardiovascular diseases and mortality, and provides protection against myocardial damage (3).resistance training (rt), which involves muscular contraction against an external force, helpsimprove or maintain muscle mass and strength, and offers beneficial physiological and clinical effectson cardiovascular diseases and related risk factors (4). a key factor in these positive effects is therelease of myokines (5). during and immediately after exercise, muscles produce and releasemolecules, cytokines, or signaling peptides known as myokines. these myokines can exert both paracrine and endocrine effects. to date, several myokines have been identified as contributing to the beneficial effects of exercise (6). one of the most well-known myokines is irisin, which is produced by skeletal muscles in response to exercise (7). irisin treatment has been shown to significantly improve cardiac function, reduce infarct size, and minimize fibrosis (8). research suggests that the underlying mechanism for these benefits is related to angiogenesis, with irisin serving as a stimulus for angiogenesis in the heart. thus, irisin may mediate the cardiac health-promoting effects of exercise training (6). vascular endothelial growth factor (vegf) is a key factor in angiogenesis, particularly under hypoxic conditions, where it stimulates cell proliferation (9). vegf promotes the recruitment of stem cells into the bloodstream and serves as a potent initiator of angiogenesis. it plays a crucial role in the migration, proliferation, matrix degradation, and formation of endothelial cell networks that contribute to vascular network formation (10). vegf is considered one of the primary mediators of angiogenesis and is influenced by physical activity (9, 11). the aim of this study was to comparatively assess vegf gene and protein expression in heart tissue, and examine its correlation with serum irisin levels, following resistance training, in comparison to exogenous irisin injection.materials and methodtwenty-one male nmri mice (5 weeks old, 18±2g) were used in this study. the mice were housed under a controlled light-dark cycle (12 hours of light, 12 hours of darkness), with a humidity level of 50-60% and a temperature of 21°c. they had ad libitum access to food and water throughout the study. the mice were randomly assigned to one of three groups: control (no intervention), resistance exercise, and irisin injection. in the resistance exercise group, training involved climbing a 1-meter-long ladder set at an 80-degree angle. the resistance training began after a 2-week period of familiarization with the training conditions and the laboratory environment. to determine the appropriate resistance for each session, the body weight of the mice was recorded. in the first week, a weight equivalent to 30% of the mice's body weight was attached to their tails. the weight was progressively increased over the course of the training period, reaching approximately 200% of their body weight by the final week. this exercise protocol consisted of 4 sets of 5 repetitions with 2 minutes of rest between sets, performed 3 times per week for 8 weeks. the irisin used in this study was in powder form, with a dose of 100 micrograms. it was dissolved in a suitable solvent and injected intraperitoneally 3 times a week, with a dose of 100 μg/kg/week. thus, the mice in the irisin group received 100 μg/kg of irisin weekly for 8 weeks. the cardiac expression of vegf gene was measured using real-time pcr, vegf protein levels were assessed by immunohistochemistry (ihc) and western blot analysis, and serum irisin concentration was evaluated using the elisa method. results from all groups were evaluated using a one-way anova test. bivariate associations between serum irisin concentration and vegf gene/protein expression in the heart were assessed using pearson’s correlation coefficient. all data are presented as the mean ± standard deviation (sd). a p-value of <0.05 was considered statistically significant.resultsirisin concentration increased in exercise and irisin groups compared to the control group (p < 0.001). no significant difference was observed between the exercise and irisin groups (p=0.755). both the resistance exercise and irisin groups showed a significant increase in vegf gene expression compared to the control group (p < 0.001). no significant difference was observed between the exercise and irisin groups (p = 0.439). data analysis showed that all experimental groups had significantly higher vegf protein expression compared to the control group (p < 0.001). the vegf protein level in the resistance training group was significantly higher than that in the irisin group (p = 0.02). both the resistance training and irisin groups demonstrated significantly higher vegf protein expression compared to the control group (p < 0.001). no significant difference was found between the exercise and irisin groups (p = 0.51). pearson’s correlation analysis revealed a positive correlation between the analyzed parameters in each group (p < 0.05 and r > 0).conclusionit appears that resistance training exerts a dynamic effect on angiogenesis in the heart, driven by complex signaling and molecular changes. this study underscores the potential role of irisin in modulating vegf expression. future research focusing on the underlying molecular mechanisms could lead to more effective and targeted treatments for cardiovascular health by targeting specific molecules or signaling pathways