تاثیر تمرین تداومی و تناوبی با مصرف مکمل اترواستاتین بر بیان mRNA 62 در رتهای سالمند دیابتی نوع ۲.

Background & Aims: Aging indicates physiological and biological changes in humans that are associated with a decrease in physical strength and cause changes in the anatomy and physiology of the body. It has been reported that at a rate of one percent per year, muscle mass decreases from the age of 30 to 60 and increases from the age of 60 onwards. The incidence of diseases such as type 2 diabetes, metabolic syndrome and cardiovascular disease, as well as chronic diseases of the musculoskeletal system and cancer are increasing, all of which can be affected by a decrease in muscle mass (1). Autophagic activity has been shown to decrease with age and may contribute to the accumulation of damaged macromolecules and organs during aging. Failure in the autophagy process exacerbates age-related diseases such as nerve damage or cancer (5). p62, a classical autophagy receptor, is a multifunctional protein located throughout the cell and involved in many signal transduction pathways, including the Keap1-Nrf2 pathway (7). p62 is an autophagy substrate used to report autophagic activity. Recently, p62 has been shown to deliver ubiquitinated proteins, including tau, to the proteasome for degradation. In addition, it can be a shuttle between the nucleus and the cytoplasm to facilitate and control the quality of cytosolic proteins (6). It has been well established that regular exercise improves physical function and brings important health benefits that inhibit many pathological diseases such as cancer as well as cardiovascular, metabolic and neurodegenerative diseases (8). Exercise promotes phenotypic adaptation in skeletal muscle, which includes mitochondrial biogenesis, angiogenesis, fiber deformation, and improved insulin sensitivity (9, 10). Regarding the effect of exercise on changes in autophagy, it has been reported that aerobic and resistance training leads to changes in autophagy indices (11, 12). Atroastetin is a type of statin that has a reducing effect on cholesterol production, as well as antioxidant, anti-inflammatory, anti-apoptotic and tissue protective effects in some pathological conditions (15-17). Study of mechanisms affecting the process of autophagy following exercise, including continuous and intermittent exercise with atroastetin supplementation can improve this process (22). Therefore, the aim of this study was to investigate the effect of eight continuous and interval exercises with atroastetin supplementation on mRNA p62 expression in elderly rats with type 2 diabetes. Methods: This is a semi-experimental study. 63 old male Wistar rats (mean weight 300 to 350 g) categorized into eight groups that included; 1) healthy control group, 2) diabetic control group, 3) diabetic group + continuous exercise, 4) diabetic group + interval exercise, 5) diabetic group + supplement, 6) diabetic group + continuous exercise + supplement, 7) diabetic group + interval exercise + supplement, and 8) saline group. Diabetes was induced by injection of 50 mg/kg streptozotocin. continuous and interval exercise program was performed, which included running at a speed of 15 to 29 meters per minute for 5 to 22 minutes for continuous aerobic exercise and six 2.5-minute sets with four minutes of rest between each set for interval exercise. Atherostatin supplementation with dose of 20 mg per kg body weight was injected intraperitoneally daily. One-way ANOVA was used for comparison between groups at the p <0.05. Results: The results showed that P62 mRNA expression was significantly reduced in all groups compared to the healthy and diabetic control group (p<0.001), but there was no significant difference between the other groups (p<0.05). (fig. 1). Conclusion: The results of the present study showed that despite the decrease in P62 mRNA expression in the experimental groups compared to the control and patient groups, no significant difference was observed between the other experimental groups. It seems that taking atroastetin supplementation, despite its anti-inflammatory and anti-oxidant effect, has no effect on the process of autophagy, which can be due to the amount used during the training period or the short-term use of atherostatin. Exercise has been reported to induce autophagy in skeletal muscle. Key autophagy proteins, including p62 and LC3-II, change significantly after exercise. These changes are consistent with an increase in autophagy after exercise. Tarawan et al. (2019) reported that exercise significantly reduced P62 in the muscles, which is more pronounced at moderate intensities. The researchers argued that at moderate intensities relative to high and low intensities, autophagic activity decreased after exercise and recommended moderate-intensity exercise (25). Exercise by phosphorylating Akt can inactivate the autophagy pathway through the PI3K-Akt-MTOR mediated pathway. Due to its unique properties, muscle fibers seem to play a significant role in the activity of autophagy and proteins involved in this process (26). Mejías et al. In the study showed that eight weeks of aerobic and resistance training in elderly men and women significantly increased LC3II / I, Atg16-12 and Bcl-2, but p62 expression decreased significantly (11, 12). Therefore, it is thought that exercise play a decisive role in inhibiting autophagy. Jamart et al. (2013) concluded that low-intensity exercise after fasting increases the activity of autophagy in skeletal muscle, which is due to a decrease in Akt pathway activity compared to satiety (27). The results of the present study showed that compared to the control and disease groups, P62 mRNA expression was significantly reduced; However, this decrease was not significant between the training groups and the training groups with supplementation. These results appear to be influenced by research methodology that the duration of the training period was insufficient or that the dose of atroastetin was low. continuous and interval exercise with atroastetin supplementation with anti-inflammatory and anti-oxidant effects on muscle cells is thought to reduce autophagy activity, resulting in a significant decrease in P62 mRNA expression compared with the patient group. In fact, exercise reduces the onset of autophagy in the skeletal muscle of diabetic rats by improving the antioxidant system and reducing the release of cytochrome c. However, the amount of reactive oxygen species has been reported to be high in animal and human species with type 2 diabetes (28). Therefore, continuous and interval exercise with atroastetin supplementation has been able to reduce autophagy markers, including P62 mRNA. There were some limitations in the present study, such as the lack of measurement of other autophagic indices such as LC3-II. It can also be noted that PI3K-Akt- MTOR autophagy pathway indices are not measured. Therefore, a study measuring these indicators in elderly samples with type 2 diabetes is recommended. According to the results, it seems that continuous and interval exercise with atherostatin supplementation can reduce P62 mRNA in elderly type 2 diabetic rats. [ABSTRACT FROM AUTHOR]