Volume 29, Issue 6 (9-2022)                   RJMS 2022, 29(6): 155-168 | Back to browse issues page

Research code: 150794
Ethics code: IR.IAU.NAJAFABAD.REC.1400.078
Clinical trials code: IR.IAU.NAJAFABAD.REC.1400.078

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Rasoolian M, Banaei Borojeni J, Farzanegi P. Effect of Two Types of Exercise Combined with Atorvastatin on PGC1α andTFAM Expression of Cardiac Myositis in Elderly Rats. RJMS 2022; 29 (6) :155-168
URL: http://rjms.iums.ac.ir/article-1-7255-en.html
Assistant Professor, Sport Medicine Research Center, Najafabad Branch, Islamic Azad University, Najafabad, Iran , Jamshid.banaii@gmail.com
Abstract:   (1626 Views)
Background & Aims: Diabetes mellitus is a common metabolic disease that occurs with high blood sugar due to a lack of insulin secretion, insulin resistance, or a combination of both (1). One of the possible mechanisms for resistance to insulin and type 2 diabetes is dysfunction and impaired mitochondrial biogenesis (3). Mitochondrial density and function are associated with cardiovascular disease, sarcopenia, insulin resistance and type 2 diabetes, the aging process, and aerobic capacity (5, 6). Today, a complete understanding of mitochondrial biogenesis is associated with an understanding of various cellular pathological conditions (7). Mitochondria play a role in increasing mitochondrial function. Quality, mitochondria represent an improvement in mitochondrial biogenesis. In tissues with high oxidative capacity, such as skeletal muscle, activated by gamma receptor joint proliferator, an alpha activated by peroxisome proliferator (PGC-1α) is considered to be the most important regulator of biogenesis and mitochondrial function (3).TFAM is a transcription and replication agent for mitochondrial DNA and plays an important role in mitochondrial biogenesis processes (8). A study by Madrasa (2018) showed that decreased expression of this group of genes is associated with decreased capacity, whole body aerobics in patients with type 2 diabetes and decreased expression of PGC-1α and nuclear genes encoding mitochondria in individuals. Insulin resistance can mean that these people have low levels of aerobic exercise (3). Exercise can play an important role in accelerating mitochondrial biogenesis, possibly leading to a reduction in mitochondrial dysfunction that occurs during the aging process, metabolic diseases such as type 2 diabetes, and conditions of muscle inactivity resisting fatigue and increasing the quality of life (7). The method of training is in the form the although metabolic control is available in type2 diabetes (25). The effect of aerobic exercise and the chemical drug atrostatin on the expression of genes affecting the mitochondrial biogenesis of cardio myositis in samples with type 2 diabetes has not been studied and because of its importance in controlling mitochondrial function following diabetes. Type 2 is impaired, it is necessary to study it, so the aim of the present study was to investigate the protective effect of continuous and intermittent exercise with atrostatin on some markers of mitochondrial biogenesis signaling myositis (PGC-1a and TFAM) in diabetic elderly rats.
Methods: Thirty-five male rats (20 weeks old) weighing between 300 and 350 g were randomly divided into 7 groups. Diabetes was induced in 6 groups. To make diabetic mice, streptozotocin (STZ) was injected intraperitoneally at a dose of 50 mg per kg body weight (26). Atorvastatin was taken orally after a meal at a dose of 2 mg per kg body weight (27). The first week of continuous training program at a speed of 15 meters per minute for five minutes, the rats started running on the treadmill. Then, every week, increasing the speed by 1 to 2 meters per minute for 1 to 2 minutes increases the running time. 48 hours after the last training session with 10 to 12 hours of night fasting, intraperitoneal injection of a combination of ketamine and xylazine was performed in anesthetized mice and tissue samples were taken. Their heart tissue was isolated and stored at -80 ° C and then transferred to a laboratory for genetic testing. To investigate the significant changes in each of the research changes between different groups, one-way analysis of variance was used and if a statistically significant difference was observed to determine the location of ANOVA, Tukey post hoc test was used. Significance level P <0.05 was considered for all calculations.
Results: In the present study, the effect of continuous and intermittent exercise combined with atorvastatin administration on PGC-1α and TFAM gene expression in cardiac myocytes of elderly diabetic rats was investigated. The first finding of the present study showed that the expression of PGC-1α gene in cardiac myocytes of rats with type 2 diabetes was significantly reduced compared to the healthy control group, while after 8 weeks of intervention, the mean PGC-1α to Significantly decreased compared to the healthy control group, while after 8 weeks of intervention, the mean PGC-1α increased in the exercise and atorvastatin groups, but in the combined intervention group, this increase was significantly greater.
Conclusion: It seems that taking atorvastatin with 8 weeks of continuous and intermittent physical activity has been able to make changes beyond taking atorvastatin alone or continuous and intermittent exercise. In this regard, Baghdam et al. (2019) by examining the effect of 8 weeks of aerobic exercise on the expression of RGC-lα gene in heart tissue in diabetic rats, concluded that aerobic exercise significantly increases the concentration of PGC-lα in heart tissue (29). However, in contrast to the findings of Chavanel et al. (2017) showed that exercise has no significant effect on the level of PGC-1α mRNA or other mitochondrial biogenesis regulators such as TFAM (30). One of the most important reasons for inconsistency in Chavanel research with the results of the present study may be the age, sex and race of the subjects as well as the type of training protocol.
PGC-lα is one of the most important transcriptional coordinator coagulators that positively regulates the expression of genes associated with metabolic and mitochondrial adaptations, thus influencing cardiac substrate selection, mitochondrial function, ATP production capacity, and species production. Reacts to oxygen (ROS). (31) Physical activity is one of the factors that trigger these messaging pathways. In other words, mitochondrial biogenesis in the cell is induced by environmental stimuli such as physical activity (30). Another result of the present study was the decrease in TFAM gene expression in cardiac myocytes of elderly diabetic rats compared to the healthy control group, while after 8 weeks of intervention, a significant increase in TFAM gene expression was observed in atorvastatin and combination groups compared to the patient group. This increase was greater in the combination of diabetic + atorvastatin + periodic exercise. It seems that when the volume of training is the same, the intensity of training can be an effective factor in the expression of TFAM; Therefore, this study showed that with a constant volume of periodic training is more effective than continuous training in the expression of TFAM gene. The present study showed that intermittent and continuous exercise with atorvastatin increased TFAM in the heart cells of elderly diabetic rats, which decreased due to diabetes and aging. Consistent with the results of the present study, Popo et al. Examined the effect of two months of aerobic exercise on skeletal muscle TFAM in human diabetic specimens and reported a significant increase (37). Therefore, the effect of the training period is enhanced at higher intensities. Exercise frequency is also one of the effective factors in increasing mitochondrial biogenesis. Chavanel et al. (2017) have shown that exercise has no significant effect on the level of mRNAPGC-1α or other mitochondrial biogenesis regulators including TFAM (30). One of the most important reasons for inconsistency in Chavanel research with the results of the present study may be in the condition of the subject and the type of muscle fiber as well as the type of training protocol. TFAM is a high-mobility transcription factor group responsible for replication and transcription of mitochondrial DNA. Impairment of the TFAM target specifically in cardiac tissue leads to a significant reduction in electron transport capacity, spontaneous cardiomyopathy, and heart failure. In contrast, increased TFAM expression in cardiac tissue protects against heart failure due to myocardial infarction.
Another finding of the present study was the positive and significant effect of atorvastatin on the expression of TFAM and PGC-1α genes in mice with type 2 diabetes. Studies show that atorvastatin improves mitochondrial function and prevents apoptosis in myocardial hypertrophy (41). In the present study, Chen et al. (2018) inhibited the decrease in the expression of PGC-1α and UCP3 in mice with myocardial insufficiency by treatment with atorvastatin (42). According to the results obtained in the present study, the effects of atorvastatin may be fundamentally different in different patients and with different races, and also its effects may vary depending on the dose or duration of use and the type of statin used. However, the effect of co-administration of atorvastatin and exercise with TFAM and PGC-1α on cardiac tissue has not been investigated. Reduces oxidative stress and inflammation in a variety of metabolic syndrome diseases such as diabetes and therefore improves these diseases by inhibiting mitochondrial damage (45). The combined use of both has more effective therapeutic effects on type 2 diabetes. The results of this study on improving heart function have been confirmed by previous studies.

 
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Type of Study: Research | Subject: Exercise Physiology

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