اثر دو شدت مختلف تمرین تناوبی همراه مصرف آلفا لیپوئیک اسید بر بیان ژن mfn بافت قلب موش‌های دارای پرفشار خونی

زمینه و هدف: پرفشارخونی به دلیل ایجاد خطرات قلبی عروقی و بیماری های کلیوی، از مهم‌ترین معضلات سلامت عمومی است. هدف از انجام تحقیق حاضر تعیین اثر دو شدت مختلف تمرین تناوبی همراه مصرف آلفا لیپوئیک اسید بر بیان ژن mfn بافت قلب موش موش‌های دارای پرفشارخونی بود.روش کار: برای انجام این تحقیق تجربی 35 سر موش نر نژاد ویستار، هشت هفته ای و وزن 190 تا 220 گرم انتخاب و پس از یک هفته آشناسازی، 5 موش به صورت تصادفی به عنوان گروه سالم جدا شده و 30 موش باقیمانده دچار پرفشارخونی شده و بصورت تصادفی در شش گروه: کنترل، تمرین تناوبی متوسط، تمرین تناوبی شدید، مکمل آلفا لیپوئیک اسید، مکمل+ تمرین تناوبی شدید، مکمل+ تمرین تناوبی متوسط تقسیم شدند. برای القای پرفشارخونی، محلول ال نیترو آرژنین متیل استر با دوز 40 میلی گرم به ازای هر کیلوگرم وزن بدن در روز و به مدت سه هفته بصورت خوراکی استفاده شد. برنامه تمرینی تناوبی با شدت بالا و متوسط به مدت شش هفته و پنج جلسه در هفته اجرا شد. به منظور مکمل دهی، روزانه ﻣﯿﺰان 20 میلی‌گرم به ازای هر کیلوگرم وزن بدن موش‌ها مکمل آلفالیپوئیک اسید لیپوزومال در متیل سلولز حل شده و یک ساعت بعد از تمرین بصورت گاواژ به موش‌ها داده شد. بیان ژن mfn2 از روش real-time pcr اندازه گیری گردید.یافته‌ها: سطح mfn2 در گروه دیابتی نسبت به گروه سالم کاهش معنی‌داری داشت (0.018=p). آلفالیپوئیک اسید (0.008=p) و تمرین تناوبی شدید+آلفالیپوئیک اسید (0.014=p) و تمرین تناوبی شدید+آلفالیپوئیک اسید (0.039=p) سطح mfn2 را به‌طور معنی‌داری نسبت به گروه دیابت افزایش دادند.نتیجه گیری: فشارخون با کاهش بیان ژن mfn2 بافت قلب همراه است و تمرین تناوبی به همراه مکمل آلفالیپوئیک اسید احتمالاً مداخله موثر در افزایش mfn2 بافت قلب در فشارخون در نظر گرفته می‌شود.

the effect of two different intensities of interval training with alpha lipoic acid consumption on the expression of mfn gene in heart tissue of rats with hypertension

background & aims: hypertension is a chronic disease that affects approximately 1 billion people worldwide and is estimated to continue to increase. high blood pressure causes long-term damage to the heart and other organs that may be potentially life-threatening and often begins at the cellular and subcellular levels (1). despite the greater understanding of the pathological processes of hypertension and the use of various drug interventions in recent years, the mortality rate of this disease is still high. therefore, new intervention strategies are needed to prevent and control pathological changes to improve high blood pressure disease. in this regard, exercise training can reduce blood pressure in hypertensive individuals and it has been shown to improve several factors involved in the pathophysiology of hypertension (9). for a long time, continuous exercise for a period of 30 minutes or more has been recommended to improve patients with high blood pressure and also to prevent this disease. however, recent studies have suggested that hiit exercises may compete with new blood pressure treatments. some studies have shown that hiit has a higher priority for improving cardiovascular fitness, endothelial function, markers of sympathetic activity, arterial stiffness, lipoproteins and blood glucose in people with hypertension (10). it has also been shown that hit leads to adaptations similar to traditional endurance training, such as increasing mitochondrial capacity and improving endurance performance (10).in addition to exercise intervention, the effect of nutritional interventions in controlling blood pressure has attracted much attention. in this regard, the consumption of antioxidants can play a significant role. alpha lipoic acid (ala) supplement is a strong antioxidant and acts as a cofactor in the mitochondrial dehydrogenase enzyme complex in metabolism (14). alpha-lipoic acid is a powerful antioxidant. this substance exerts its antioxidant effect by directly clearing free radicals and chelating metal ions, as well as affecting other antioxidants and increasing intracellular glutathione (15). alpha-lipoic acid and dehydro-alpha-lipoic acid reduce oxidative damage by their cooperative action and through the activation of the antioxidant system and the regeneration of endogenous antioxidants (16). therefore, the researcher is trying to discover the question of whether there is a difference between the effect of two different intensities of interval training with alpha lipoic acid consumption on mfn2 gene expression in the heart tissue of rats with hypertension?methods: to carry out this experimental research, 35 eight-week-old male wistar rats weighing 190 to 220 grams were selected and after one week of familiarization, 5 rats were randomly separated as the healthy group and the remaining 30 rats were hypertensive. they were randomly divided into six groups: control, moderate interval training, intense interval training, alpha lipoic acid supplement, supplement + intense interval training, supplement + moderate interval training. to induce high blood pressure, l-nitroarginine methyl ester solution was used orally at a dose of 40 mg per kilogram of body weight per day for three weeks. high and medium intensity interval training program was implemented for six weeks and five sessions per week. for the purpose of supplementation, 20 mg of liposomal alpha lipoic acid supplement per kilogram of body weight was dissolved in methyl cellulose and given to the rats by gavage one hour after training. real-time pcr method for the relative expression of mrna of mfn2 gene were used. at the end, descriptive statistics (mean and standard deviation) and shapiro-wilk tests, one-way analysis of variance and tukey's follow-up at a significance level of p<0.05 were used for statistical analysis of the data using spss version 23 software. became.results: the average weight of the subjects is presented using descriptive statistics. the results showed all the mice are in a certain range, which indicates their homogeneity. the results of the one-way variance test showed a significant difference between the mfn2 gene expression in the heart tissue of different groups (f=3.821, p=0.018). the results of tukey's post hoc test showed that the expression of the mfn2 gene in the heart tissue was significantly decreased in the hypertension group compared to the healthy group (p=0.018). compared to the blood pressure group, ala supplementation (p=0.008), moderate exercise+supplement (p=0.039) and intense exercise+supplement (p=0.014) increased the expression of mfn2 gene in heart tissue. an interesting point is that intense interval training (p=0.991) and moderate training (p=0.916) led to a non-significant increase compared to the blood pressure group. no significant difference was observed between other groups (p>0.05).cocclusion: the results of the present study showed that six weeks of intense and moderate intermittent exercise did not change the expression of the mfn2 gene in the heart tissue in hypertensive rats. the exact mechanism of control of mitochondrial regeneration in hypertension is not clear. however, it seems that reactive oxygen species (ros) play an important regulatory role in this process. sports activity can lead to the production of mitochondrial ros, and as a result, the expression of mitochondrial fission and fusion proteins increases. as recent evidence has shown that oxidative stress increases mitochondrial fission. however, it should be noted that apparently the role of ros in mitochondrial fission depends on the amount and duration of exposure. based on this, it seems that different intensities of sports activity are associated with different levels of ros increase and subsequently affect protein fission and fusion. despite the different effects of sports activity on the production of ros and antioxidant defense, however, doing bouts and sessions of sports activity in long-term training protocols also leads to a transient increase in ros, which is probably dependent on the intensity and duration of the sports activity. based on the findings of the present study, exercise intensity was not a factor affecting the mitochondrial dynamics of heart tissue, so that none of the moderate and high intensity intermittent exercise did not change the indices of mitochondrial dynamics. few studies have been conducted regarding the effect of training intensities on mitochondrial dynamics. in this regard, demirchi et al. showed that moderate intensity interval training had a better effect on mitochondrial dynamic indices than intense interval training. it is possible that moderate intensity interval training has led to optimal production of ros, which has more favorable effects than high and low intensity exercise on mfn2 proteins, so that high intensity interval exercise with an increase in high concentration of ros leads to a reduction in the effects. material and exercise as well as intermittent exercise with moderate intensity with much lower levels did not lead to reaching the desired threshold in order to stimulate proteins related to mitochondrial dynamics.