تأثیر یک دوره تمرین استقامتی همراه با مصرف آتورواستاتین بر برخی هورمون های جنسی و نشانگرهای تولیدمثلی موش های صحرایی نر ویستار (مقاله علمی وزارت علوم)
درجه علمی: نشریه علمی (وزارت علوم)
آرشیو
چکیده
زمینه و هدف: استفاده همزمان از داروهای استاتینی و تمرینات استقامتی ممکن است اثربخشی بهتری در درمان و پیشگیری از ناهنجاری های قلبی-عروقی از قبیل انفارکتوس میوکارد داشته باشد. هدف از پژوهش حاضر، بررسی اثر ترکیب تمرینات ورزشی استقامتی و مصرف داروی آتورواستاتین بر ویژگی های اسپرم و سطح هورمون های جنسی سرم موش های صحرایی نر نژاد ویستار مبتلا به آنفارکتوس میوکارد بود. روش تحقیق: تعداد 28 سر موش صحرایی نر نژاد ویستار با وزن 250-210 گرم، به طور تصادفی به چهار گروه مساوی (هفت سر موش در هر گروه) کنترل، آتورواستاتین، تمرین استقامتی، و آتورواستاتین+ تمرین استقامتی تقسیم شدند. برای ایجاد انفارکتوس میوکارد، از تزریق زیرجلدی ایزوپرنالین به میزان 150 میلی گرم/کیلوگرم وزن بدن در دو روز متوالی، استفاده شد. پس از القاء انفارکتوس میوکارد، برنامه تمرینی و مداخله دارویی آغاز گردید. برنامه تمرین ورزشی شامل دویدن روی نوارگردان (با سرعت 16-10 متر بر دقیقه و 50-10 دقیقه در روز) به مدت هشت هفته، پنج روز در هفته بود. گروه های آتورواستاتین و آتورواستاتین+ تمرین ورزشی؛ روزانه میزان 10 میلی گرم/کیلوگرم آتورواستاتین به صورت گاواژ دریافت کردند. 48 ساعت پس از آخرین جلسه تمرین، خون گیری و تشریح انجام شد. اندازه گیری شاخص های سرمی با روش الایزا صورت گرفت. همچنین برای ارزیابی ویژگی های اسپرم ها، اپیدیدیم از بافت بیضه جدا و مورد بررسی قرار گرفت. نتایج با استفاده از آزمون تحلیل واریانس یک راهه و شفه در سطح معنی داری 05/0≥p استخراج گردید. یافته ها: تمرین استقامتی، مصرف آتورواستاتین و ترکیب تمرین و دارو، باعث کاهش معنی دار در تعداد اسپرم، درصد اسپرم های زنده، میزان تحرک اسپرم ها، سطح تستوسترون، هورمون لوتئینی (LH)، هورمون محرک فولیکول (FSH)، لیپوپروتئین با چگالی پایین (LDL)، کلسترول و تری گلیسرید سرمی؛ و افزایش معنی دار لیپوپروتئین با چگالی بالا (HDL) در رت های مبتلا به آنفارکتوس میوکارد شد. نتیجه گیری: تمرین استقامتی، مصرف آتورواستاتین و ترکیب آن ها، اگر چه موجب بهبود نیم رخ لیپیدی گردید، اما بر سطوح هورمون های جنسی، نشانگرهای اسپرمی و در نتیجه عملکرد تولیدمثلی موش های صحرایی نر مبتلا به آنفارکتوس میوکارد؛ اثر نامطلوب داشت.The effect of a course of endurance training with atorvastatin on some sex hormones and reproductive markers of male Wistar rats
Background and Aim: Statins have specific effects on various body tissues in pathological conditions (3, 4). One of the most widely used statins is atorvastatin, which is used to treat and prevent cardiovascular abnormalities and also to treat high blood lipids (1, 7). A significant side effects of atorvastatin is the reduction of testosterone production. Researchers has demonstrated that endurance training has an acute effect on hormonal response and chronic changes in basal hormone concentrations (16). Results indicate that endurance training reduces plasma cholesterol concentrations (17). Additionally, it has been shown that endurance training is associated with a decrease in testosterone levels (14).Considering atorvastatin’s role in inhibiting cholesterol synthesis and the impact of endurance training in reducing plasma cholesterol concentration, along with the necessity of cholesterol for the synthesis of sex hormones, it appears that the simultaneous use of endurance training and statin drugs can cause disorders in the production of sex hormones through cholesterol reduction and ultimately reduce reproductive function. Therefore, the present study investigates the combined effects of endurance training and atorvastatin on sperm characteristics and sex hormone levels of male rats with myocardial infarction. Materials and Methods: Twenty-eight male Wistar rats, weighing 210-250 g were prepared and divided into four groups: control, atorvastatin, endurance training, and atorvastatin combined with endurance training. All rats were maintained in standard environmental conditions with free access to water and food.To induce myocardial infarction, rats were injected subcutaneously with 150 mg/kg of isoprenaline hydrochloride (Sigma, USA) daily for two days at 24-hour intervals (25). The control group received normal saline instead of isoprenaline for two days. Forty-eight after the induction of myocardial infarction, the exercise program and drug intervention began. The exercise program included treadmill running at a speed of 10-16 m/min for 10-50 minutes per day, five days a week, over a duration of eight weeks (26). The drug intervention groups received 10 mg/kg of atorvastatin dissolved in normal saline daily orally and by gavage. The other groups also received normal saline in the same amount. Forty-eight hours after the last training session, the rats were anesthetized and blood was collected from their hearts. The blood samples were then centrifuged and their serum was separated and stored at -30°C for measurement of biochemical factors. The ELISA method was used to measure the levels of serum factors. To evaluate sperm characteristics, including sperm count, viability, and motility, the animals were dissected and their epididymis were separated from the testicular tissue and was examined. All data were analyzed using SPSS software (version 22). A one-way analysis of variance (ANOVA) was performed, followed by the Scheffé post hoc test to compare differences between groups. A level of p≤0.05 was considered statistically significant.Findings: The results of the sperm count indicated that sperm count in the experimental groups (atorvastatin (32.15±3.11), endurance training (34.01±2.72) and combination group (33.57±2.01) decreased significantly compared to the control group (49.41±2.28). However, there was no significant difference in sperm count among the experimental groups.The analysis of live sperm count revealed that the percentage of live sperm in the experimental groups (atorvastatin: 63.47±3.01, endurance training: 65.41±2.83, and combination group: 64.12±2.12) also decreased significantly compared to the control group (83.25±2.74). Again, the differences in the percentage of live sperm among the experimental groups were not significant.The results of the sperm motility showed that the rapid sperm motility rate in the experimental groups (atorvastatin, endurance training, combination) decreased compared to the control group, but the decrease was significant only in the atorvastatin and endurance training groups compared to the control group. The rapid sperm motility rate in the combination group was significantly different compared to the atorvastatin and exercise groups. Additionally, the percentage of non-motile sperm in the atorvastatin and exercise groups increased significantly compared to the control group. There was no significant difference between the combination group and the control group in terms of the percentage of non-motile sperm.The results also indicated that the serum levels of testosterone, Luteinizing hormone (LH) and Follicle-stimulating hormone (FSH) in the endurance training group, the atorvastatin group and the combination group decreased significantly compared to the control group. Furthermore, the serum levels of HDL in the endurance training group, atorvastatin group, and the combination of endurance training and atorvastatin increased significantly compared to the control group. In contrast, the serum levels of LDL and cholesterol decreased significantly compared to the control group. The serum levels of triglycerides in the endurance training group decreased significantly compared to the control group.Conclusion: The results of the present study demonstrated that while endurance training, atorvastatin and their combination improved lipid profile and reduced total cholesterol, they simultaneously caused disturbances in sperm parameters (sperm count, live sperm count and sperm motility) and decreased levels of sex hormones (testosterone, LH and FSH) in male rats with myocardial infarction. It seems that the decrease in testosterone levels in the exercise and drug intervention groups in the present study is probably due to the effects of endurance training and atorvastatin on reducing cholesterol (a precursor of steroid hormones), which will disrupt the spermatogenesis process and, as a result, further reduce the number of spermatogonial cells. Such changes can lead to a decrease in reproductive activity in males. Therefore, in situations where there is concern about infertility and reduced reproductive function, it is advisable to avoid the simultaneous and long-term use of statin drugs and endurance training. Alternative approaches should be considered to improve the lipid profile and reduce the risk of cardiovascular diseases.Keywords: Exercise training, Atorvastatin, Infertility, Myocardial infarction. Ethical considerations: This study has received ethical approval with the ID number IR.ILAM.REC.1402.002 from the Research Ethics Committee of Ilam University.Compliance with ethical guideline: In this study, all experiments were conducted in accordance with the regulations of the Research Ethics Committee of Ilam University for animal studies.Funding: This research project was funded by the Iran’s National Elites Foundation (Contract No. 841/4890).Conflict of interest: None of the authors of this article have any conflicts of interest for its publication.