نوع مقاله : مقاله پژوهشی

نویسندگان

• الهه پیرعلائی ¹
• غلامرضا حمیدیان ²
• زهرا مهری رخ ³
• علیرضا رشیدپور ⁴
• مرتضی نیک خصال ⁵

¹ دانشیار گروه فیزیولوژی ورزشی، دانشکده تربیت بدنی و علوم ورزشی، دانشگاه تبریز، تبریز، ایران.

² دانشیار گروه علوم پایه، دانشکده دامپزشکی، دانشگاه تبریز، تبریز، ایران.

³ دانشجوی کارشناسی ارشد فیزیولوژی ورزشی، دانشکده تربیت بدنی و علوم ورزشی، دانشگاه تبریز، تبریز، ایران.

⁴ دانشجوی دکتری فیزیولوژی ورزشی، دانشکده تربیت بدنی و علوم ورزشی، دانشگاه تبریز، تبریز، ایران.

⁵ دکتری فیزیولوژی ورزشی، دانشکده تربیت بدنی و علوم ورزشی، دانشگاه تبریز، تبریز، ایران.

چکیده

زمینه و هدف: میکرو RNAها و مکمل‌های آنتی‌اکسیدانی به‌عنوان اهداف درمانی بالقوه برای عوارض قلبی‌عروقی و هایپرگلیسمی ناشی از دیابت مطرح شده‌اند. این مطالعه به بررسی اثر تمرین هوازی همراه با عصاره هیدروالکلی میوه قره‌‌قات بر شاخص‌‌های گلایسمیک و بیان miR-195 در بافت قلبی رت‌های مبتلا به دیابت نوع دو پرداخته است. روش تحقیق: تعداد 24 موش‌‌های صحرایی نر نژاد ویستار (میانگین وزنی 20±200 گرم و سن هشت هفته) به‌طور تصادفی به چهار گروه کنترل دیابتی، دیابتی+مکمل، دیابتی+تمرین، و دیابتی+مکمل+تمرین تقسیم شدند. دیابت نوع دو با تغذیه رژیم پرچرب و تزریق استرپتوزوتوسین القا شد. گروه‌های دریافت‌کننده مکمل، روزانه ۲۵۰ میلی‌گرم بر کیلوگرم از وزن بدن عصاره قره‌‌قات دریافت کردند. پروتکل تمرینی شامل دویدن روی نوارگردان با سرعت ۱۸ تا ۲۴ متر در دقیقه، به مدت ۳۰ تا ۶۰ دقیقه به مدت هشت هفته و پنج روز در هفته اجرا شد. پس از پایان مداخله، گلوکز، انسولین، مقاومت به انسولین و miR-195 بافت قلبی اندازه‌‌گیری شد. برای تحلیل داده‌‌ها از آزمون آماری آنالیز واریانس یک‌‌راهه با استفاده از نرم‌‌افزار SPSS در سطح معنی‌‌داری 05/0>p استفاده شد. یافته‌ها: پس از هشت هفته مداخله، گلوکز خون ناشتا و مقاومت به انسولین در تمامی گروه‌های مداخله نسبت به گروه کنترل دیابتی کاهش معنی داری نشان داد (p=0/001). سطح انسولین در گروه‌های دریافت‌کننده مکمل نسبت به گروه‌های دیابتی و تمرین به‌تنهایی، به‌طور معنی داری کاهش یافت (به ترتیب با p=0/002، p=0/001). بیان miR-195 در تمامی گروه‌های دیابتی+مکمل، دیابتی+تمرین و دیابتی+مکمل+تمرین؛ نسبت به گروه کنترل دیابتی، کاهش معنی داری داشت ( به ترتیب با p=0/001، p=0/001 ،p=0/01). نتیجه‌گیری: هر دو مداخله تمرین هوازی و مکمل‌‌دهی قره‌‌قات باعث بهبود شاخص‌‌های گلایسمیک و بیان miR-195 می‌‌شوند؛ و ترکیب مکمل‌‌دهی قره‌‌قات با تمرین هوازی اثرات مطلوب‌‌تری بر بیان miR-195 بافت قلبی موش‌‌های صحرایی دیابتی نوع دو دارد. 

کلیدواژه‌ها

• تمرین هوازی
• دیابت نوع دو
• قره‌‌قات
• miR-195

عنوان مقاله [English]

Effect of aerobic training supplementation with the hydroalcoholic extract of Qaraqat fruit on glycemic indices and MiR-195 expression in the cardiac tissue of type II diabetic rats

نویسندگان [English]

• Elaheh Piralaiy ¹
• Gholamreza Hamidian ²
• Zahra Mehri Rokh ³
• Alireza Rashidpour ⁴
• Morteza Nikkhesal ⁵

¹ Associate Professor at Department of Exercise Physiology, Faculty of Physical Education and Sport Sciences, University of Tabriz, Tabriz, Iran.

² Associate Professor at Department of Basic Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran.

³ MSc in Exercise Physiology, Faculty of Physical Education and Sports Sciences, University of Tabriz, Tabriz, Iran.

⁴ PhD Student in Exercise Physiology, Faculty of Physical Education and Sports Science, University of Tabriz, Tabriz, Iran.

⁵ PhD in Exercise Physiology, Faculty of Physical Education and Sports Science, University of Tabriz, Tabriz, Iran.

چکیده [English]

Extended Abstract
Background and Aim: Cardiovascular diseases linked to diabetes are among the leading causes of mortality worldwide (1). According to the latest global data from the International Diabetes Federation (IDF) in 2019, approximately 463 million people are living with diabetes. This figure is expected to rise substantially by 2045, with projected increases of 143% in Africa, 96% in the Middle East and North Africa, 74% in Southeast Asia, and 55% in South and Central America (2).
Recently, microRNAs have emerged as promising therapeutic targets for diabetes-induced cardiovascular complications (3). Research indicates that dysregulated microRNA expression is associated with various pathological conditions of the myocardium, including hypertrophy, fibrosis, apoptosis, arrhythmia, and heart failure (4). Notably , miR-195 has been associated with cardiac failure and hypertrophy, with its inhibition preventing apoptosis in palmitate-stimulated cardiomyocytes while its overexpression leads to cardiac failure and hypertrophy (5).
The interaction between miR-195 and oxidative stress in diabetes suggests a bidirectional relationship, where oxidative stress influences miR-195 biogenesis and function, while dysregulated miR-195 expression exacerbates oxidative stress levels. Gaining a deeper understanding of miR-195’s role in oxidative stress could offer valuable insights into the pathogenesis of diabetes and its complications, potentially paving the way for targeted therapeutic interventions.
Materials and Methods: This experimental-applied intervention study was conducted at the Faculty of Veterinary Medicine, University of Tabriz, between April to August 2023. Twenty-four male Wistar rats (weight: 200 ± 20 g, age: 8 weeks) were randomly assigned to four groups (n= 6 per group): diabetic control (DC), diabetic + supplementation (DS), diabetic + exercise (DE), and diabetic + supplementation + exercise (DSE). The animals were housed in polyethylene cages under controlled conditions, including a temperature of 20–22 °C, a 12:12-hour light-dark cycle, and humidity levels of 55–65%. Type ॥ diabetes was induced by feeding the rats a high-fat diet (60% fat) for two weeks, followed by an intraperitoneal injection of streptozotocin (35 mg/kg body weight). Diabetes was confirmed when fasting blood glucose levels exceeded 250 mg/dL.
The exercise protocol involved treadmill running for eight weeks, five days per week. Each session consisted of a five-minute warm-up and cool-down period, with the main exercise intensity progressively increasing from 18 to 24 m/min over 30–60 minutes (26). The supplemented groups received a daily oral gavage of hydroalcoholic Qaraqat fruit extract (250 mg/kg body weight).
For tissue analysis, the rats were anesthetized with a combination of ketamine (90 mg/kg) and xylazine (10 mg/kg) after 12–14 hours of fasting period. Cardiac tissue samples were collected for miR-195 expression analysis using real-time PCR. Blood glucose levels were measured using the glucose oxidase method, while insulin concentrations were determined via ELISA. Insulin resistance was calculated using the HOMA-IR formula.
Findings: The eight-week intervention period led to significant improvements across multiple parameters.
Glycemic Control: Fasting blood glucose levels significantly decreased in all intervention groups compared to the diabetic control group (p=0.001), with the combined intervention group showing the greatest reduction. Both supplementation groups demonstrated better glycemic control than the exercise-only group.
Insulin Parameters: Insulin levels were significantly reduced in the supplementation groups compared to both the diabetic control and exercise-only groups (p=0.001, p=0.002, respectively). Insulin resistance (HOMA-IR) significantly decreased in all intervention groups compared to the diabetic control group (p=0.001), with the combined intervention showing the most favorable effects on insulin sensitivity.
Cardiac miR-195 Expression: A significant decrease in miR-195 expression was observed in all intervention groups compared to the diabetic control group (p=0.001, p=0.01, p=0.001 for the supplementation, exercise, and combined groups, respectively). The combined intervention group demonstrated a more pronounced reduction in miR-195 expression than the exercise-only group (p = 0.02). Additionally, supplementation alone had a stronger effect on miR-195 expression compared to exercise alone (Fig 1).
Body Weight and Physical Parameters: The exercise groups showed better weight management compared to the non-exercise groups. No adverse effects were observed in any of the intervention groups, and all interventions were well tolerated by the animals.
Conclusion: The findings of this study demonstrate that both aerobic exercise and Qaraqat supplementation, whether administered separately or in combination, could effectively improve glycemic indices and reduce miR-195 expression in the cardiac tissue of type ॥ diabetic rats. Notably, the combined intervention exhibited a more pronounced effect on cardiac miR-195 expression compared to individual treatments, suggesting a potential synergistic effect.  
The significant reduction in miR-195 expression, particularly in the combined intervention group, highlights a possible protective mechanism against diabetes-induced cardiac complications. This effect, alongside improved glycemic control and enhanced insulin sensitivity, suggests that the integration of aerobic exercise with Qaraqat supplementation could serve as a comprehensive therapeutic strategy for managing type II diabetes and mitigating its cardiovascular complications.  
These findings carry important clinical implications, indicating that incorporating regular aerobic exercise with Qaraqat supplementation may provide an effective approach for diabetes management and cardiovascular disease prevention. Keywords: Aerobic Training, miR-195, Qaraqat, Type II Diabetes, Cardiac Tissue.
Ethical Considerations: This study was conducted following laboratory animal work guidelines and with approval from the University of Tabriz Ethics Committee (IR.TABRIZU.REC.1402.022). All procedures were performed in accordance with ethical standards for animal research.
Funding: No external funding was received for this research.
Conflicts of Interest: The authors declare no conflicts of interest.

کلیدواژه‌ها [English]

• mir-195
• Qaraqat
• Type 2 diabetes