تأثیر تمرین هوازی با مکمل عصاره هیدروالکلی میوه قره قات بر شاخص های گلایسمیک و بیان miR-195 در بافت قلب موش های صحرایی دیابتی شده نوع دو (مقاله علمی وزارت علوم)
درجه علمی: نشریه علمی (وزارت علوم)
آرشیو
چکیده
زمینه و هدف: میکرو RNAها و مکمل های آنتی اکسیدانی به عنوان اهداف درمانی بالقوه برای عوارض قلبی عروقی و هایپرگلیسمی ناشی از دیابت مطرح شده اند. این مطالعه به بررسی اثر تمرین هوازی همراه با عصاره هیدروالکلی میوه قره قات بر شاخص های گلایسمیک و بیان miR-195 در بافت قلبی رت های مبتلا به دیابت نوع دو پرداخته است. روش تحقیق: تعداد 24 موش های صحرایی نر نژاد ویستار (میانگین وزنی 20±200 گرم و سن هشت هفته) به طور 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. گروه های دریافت کننده مکمل، روزانه ۲۵۰ میلی گرم بر کیلوگرم از وزن بدن عصاره قره قات 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 اندازه گیری شد. برای تحلیل داده ها از آزمون آماری آنالیز واریانس یک راهه با استفاده از نرم افزار SPSS در سطح معنی داری 05/0>p استفاده شد. یافته ها: پس از هشت هفته مداخله، گلوکز خون ناشتا و مقاومت به انسولین در تمامی گروه های مداخله نسبت به گروه کنترل دیابتی کاهش معنی داری نشان داد (p=0/001). سطح انسولین در گروه های دریافت کننده مکمل نسبت به گروه های دیابتی و تمرین به تنهایی، به طور معنی داری کاهش یافت (به ترتیب با p=0/002، p=0/001). بیان miR-195 در تمامی گروه های 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). نتیجه گیری: هر دو مداخله تمرین هوازی و مکمل دهی قره قات باعث بهبود شاخص های گلایسمیک و بیان miR-195 می شوند؛ و ترکیب مکمل دهی قره قات با تمرین هوازی اثرات مطلوب تری بر بیان miR-195 بافت قلبی موش های صحرایی دیابتی نوع دو دارد.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
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.
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