تأثیر شش هفته تمرین استقامتی بر بیان پروتئین سینتافیلین در بافت نخاع موش‌های صحرایی مبتلا به نوروپاتی دیابتی تجربی

نوع مقاله : مقاله پژوهشی

نویسندگان

1 دانشجوی دکتری، گروه فیزیولوژی ورزشی، دانشگاه تهران، پردیس بین المللی کیش، ایران.

2 دانشیار، گروه فیزیولوژی ورزش، دانشکده تربیت بدنی و علوم ورزشی، دانشگاه تهران، تهران، ایران.

3 استاد، گروه فیزیولوژی ورزشی، دانشکده تربیت بدنی و علوم ورزشی، دانشگاه خوارزمی، تهران، ایران.

4 دانشیار، گروه علوم ورزشی، دانشکده ادبیات و علوم انسانی، دانشگاه ولی‌عصر (عج)، رفسنجان، ایران.

10.22123/chj.2022.282939.1716

چکیده

مقدمه: نوروپاتی از عوارض شایع دیابت شیرین است. پروتئین سینتافیلین (Syntaphilin) در فرآیند لنگرکردن (Anchoring) میتوکندری با میکروتوبول­ها نقش دارد. هدف از پژوهش حاضر، تعیین تأثیر شش هفته تمرین استقامتی بر بیان پروتئین سینتافیلین در بافت نخاع موش­های صحرایی مبتلا به نوروپاتی دیابتی تجربی بود.
مواد و روش‌ها: 40 سر موش صحرایی به صورت تصادفی به چهار گروه تقسیم شدند (دیابتی کنترل (DC)- دیابتی تمرین (DT)- کنترل سالم (HC)- تمرین سالم (HT)). القای دیابت با تزریق درون صفاقی محلول استرپتوزوسین (Streptozotocin) (45 میلی‌گرم/کیلوگرم) انجام شد. تمرین استقامتی به مدت شش هفته اجرا شد. آزمون­های Tail-Flick و Von Frey برای سنجش پردردی حرارتی و آلوداینیای مکانیکی استفاده گردید. بررسی بیان سینتافیلین با روش ایمونوهیستوشیمی صورت گرفت. داده­ها توسط آنالیز واریانس دو راهه تجزیه و تحلیل شدند.
یافته ­ها: آزمون­های Tail-Flick و Von Frey کاهش معنی­داری در آستانه حس درد در گروه‌های دیابتی نسبت به غیردیابتی نشان دادند. پس از تزریق STZ، قندخون در گروه‌های دیابتی نسبت به غیردیابتی به صورت معنی­داری افزایش یافت (05/0p<). در پایان پژوهش، وزن گروه‌های دیابتی نسبت به غیردیابتی کاهش معنی­داری داشت (05/0p<). همچنین تفاوت معنی­داری در بیان سینتافیلین بین گروه‌های HT، DC و DT با گروه HC (001/0p=)، بین گروه‌های HT و DT با گروه DC (001/0p=) و بین گروه HT با گروه DT (002/0p=) وجود داشت.
نتیجه ­گیری: تمرین استقامتی موجب بهبود پاسخ­های درد نوروپاتیک و افزایش بیان سینتافیلین در نخاع موش­های مبتلا به نوروپاتی دیابتی شد. این یافته­ها می­تواند به عنوان یک شیوه درمانی برای عوارض نوروپاتی دیابتی استفاده شود.

کلیدواژه‌ها


عنوان مقاله [English]

The Effect of Six Weeks of Endurance Training on Syntaphilin Protein Expression in Spinal Cord Tissue of Rats with Experimental Diabetic Neuropathy

نویسندگان [English]

  • A Kooshesh 1
  • MR Kordi 2
  • H Rajabi 3
  • AR Kazemi 4
1 PhD student, Dept of Exercise physiology, Kish International Campus, University of Tehran, Kish Island, Iran.
2 Associate Prof, Dept of Sports Physiology, Faculty of Physical Education and Sport Sciences, University of Tehran, Tehran, Iran.
3 Prof, Dept of Sports Physiology, Faculty of Physical Education and Sports Sciences, Kharazmi University, Tehran, Tehran, Iran.
4 Associate Prof, Dept of Sports Science, Faculty of Literature and Humanities, Valiasr University, Rafsanjan, Iran.
چکیده [English]

Introduction: Neuropathy is a common complication of diabetes mellitus. Syntaphillin is involved in the anchoring of mitochondria to microtubules. The present study aimed to investigate the effect of six weeks of endurance training on Syntaphillin expression in spinal cord tissue of rats with experimental diabetic neuropathy.
Materials and Methods: 40 rats were randomly divided into four groups, diabetes control (DC), diabetes training (DT), healthy control (HC), and healthy training (HT). Induction of diabetes was performed by intraperitoneal injection of the Streptozotocin solution (45 mg/kg). Endurance training was performed for six weeks. Tail-Flick and Von Frey tests were used to measure thermal hyperalgesia and mechanical allodynia. The expression of Syntaphillin was evaluated by immunohistochemistry. The data were analyzed using two-way ANOVA.
Results: Teal-flick and von-Frey tests showed that pain threshold was significantly reduced in diabetic groups compared to non-diabetic groups (p<0.05). After STZ injection, blood glucose in diabetic groups increased significantly compared to non-diabetic groups (p<0.05). At the end of the study, the weight of diabetic groups decreased significantly compared to non-diabetic groups (p<0.05). In addition, there was a significant difference in the expression of Syntaphilin between HT, DC, and DT groups with HC group (p=0.001), between HT and DT groups with DC group (p=0.001) and between HT group and DT group (p=0.002).
Conclusion: Endurance training improves neuropathic pain responses and increases the Syntaphilin expression in the spinal cord of diabetic rats. These findings can be considered as a treatment for the complications of diabetic neuropathy.

کلیدواژه‌ها [English]

  • Diabetic Neuropathy
  • Syntaphilin
  • Endurance Training
  • Rat
  • Streptozotocin
  1. Yokoyama H, Araki SC, Kawai K. Yamazaki K, Tomonaga O, Shirabe S, et al. Declining trends of diabetic nephropathy, retinopathy and neuropathy with improving diabetes care indicators in Japanese patients with type 2 and type 1 diabetes (JDDM 46). BMJ Open Diabetes Research & Care 2018;6(1):e000521.
  2. Garcia-Martin E, Cipres M, Melchor I, Gil-Arribas L, Vilades E, Polo V, et al. Neurodegeneration in patients with type 2 diabetes mellitus without diabetic retinopathy. Journal of Ophthalmology 2019; 2019:1-8
  3. Kim HG. Cognitive dysfunctions in individuals with diabetes mellitus. YUJM 2019;36(3):183–191.
  4. Kara A, Unal D, Simsek N, Yucel A, Yucel N, Selli Ultra-structural changes and apoptotic activity in cerebellum of post-menopausal-diabetic rats: a histochemical and ultra-structural study. Gynecological Endocrinology 2014;30(3):226-231.
  5. Pop-Busui R, Boulton AJ, Feldman EL, Bril V, Freeman R, Malik RA, et al. Diabetic neuropathy: a position statement by the American Diabetes Association. Diabetes care 2017;40(1);136-154.
  6. Svitkina, T. The actin cytoskeleton and actin-based motility. CSH Perspective 2018;10(1):a018267.
  7. Das S, Boczan J, Gerwin C, Zald PB, Sheng ZH, et al. Regional and developmental regulation of syntaphilin expression in the brain: a candidate molecular element of synaptic functional differentiation. Molecular Brain Research 2003;116(1-2):38-49.
  8. Ballatore C, Lee VM, Trojanowski JQ. Tau-mediated neurodegeneration in Alzheimer's disease and related disorders. NRN 2007;8(9):663-672.
  9. Vaynman S, Ying Z, Gomez‐Pinilla F. Hippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition. EJN 2004;20(10):2580-2590.
  10. El-Sayes J, Harasym D, Turco CV, Locke MB, Nelson AJ. Exercise-induced neuroplasticity: a mechanistic model and prospects for promoting plasticity. Neuroscientist 2019;25(1):65-85.
  11. Jenkins DW, Jenks A. Exercise and diabetes: a narrative review. foot & Ankle Surgery 2017;56(5):968-974.
  12. Amiri Parsa T, Attarzadeh Hosseini SR, Bijeh N, Hamedi Nia MR. The effect of combined exercise (resistance-aerobic) valume on neurotrophic changes, neuropathic pain and some performance indicators in postmenopausal women with diabetic peripheral neuropathy. IJOGI 2020;22(12):24-37. [Persian]
  13. Cruccu G, Truini A. A review of neuropathic pain: from guidelines to clinical practice. Pain and Therapy 2017;6(1):35-42.
  14. Islam M, Code QR. Streptozotocin is more convenient than Alloxan for the induction of Type 2 diabetes. IJPR 2017;7(01):06-11.
  15. Høydal MA, Wisløff U, Kemi OJ, Ellingsen Ø. Running speed and maximal oxygen uptake in rats and mice: practical implications for exercise training. EJPC 2007;14(6):753-760.
  16. Chae CH, Jung SL, An SH, Park BY, Wang SW, Cho IH, et al. treadmill exercise improves cognitive function and facilitates nerve growth factor signaling by activating mitogen-activated protein kinase/extracellular signal-regulated kinase1/2 in the streptozotocin-induced diabetic rat hippocampus (retraction of vol 164, pg 1665, 2009). neuroscience 2013;231:445.
  17. Gebhart GF, Schmidt RF. Encyclopedia of pain. 2nd ed. Springer, Berlin, Heidelberg: 2013;3832-3832.
  18. Taherabadi SJ, Rahmati M, Mirnasuri R. Effect of endurance training on cerebellar gene expression of the ADP-ribosylation factor 6 in rats with diabetic peripheral neuropathy. ZJRMS 2018;20(12): e84106.
  19. Stagg NJ, Mata HP, Ibrahim MM, Henriksen EJ, Porreca F, Vanderah TW, et al. Regular exercise reverses sensory hypersensitivity in a rat neuropathic pain model: role of endogenous opioids. Anesthesiology 2011;114(4): 940-948.
  20. Sharma NK, Ryals JM, Gajewski BJ, Wright DE. Aerobic exercise alters analgesia and neurotrophin-3 synthesis in an animal model of chronic widespread pain. PTJ 2010;90(5):714-725.
  21. Rossi DM, Valenti VE, Navega MT. Exercise training attenuates acute hyperalgesia in streptozotocin-induced diabetic female rats. Clinics 2011;66:1615-1619.
  22. Mazzardo-Martins L, Martins DF, Marcon R, Dos Santos UD, Speckhann B, Gadotti VM, et al. High-intensity extended swimming exercise reduces pain-related behavior in mice: involvement of endogenous opioids and the serotonergic system. Journal of Pain 2010;11(12):1384-1393.
  23. Sluka KA, Rasmussen LA. Fatiguing exercise enhances hyperalgesia to muscle inflammation. Pain 2010;148(2):188-197.
  24. Chen YW, Li YT, Chen YC, Li ZY, Hung CH. Exercise training attenuates neuropathic pain and cytokine expression after chronic constriction injury of rat sciatic nerve. Anesthesia & Analgesia 2012;114(6):1330-1337.
  25. Cunha JM, Funez MI, Cunha FD, Parada CA, Ferreira SH. Streptozotocin-induced mechanical hypernociception is not dependent on hyperglycemia. BJMBR 2009;42(2):197-206.
  26. Tsou YH, Shih CT, Ching CH, Huang JY, Jen CJ, Yu L, et al. Treadmill exercise activates Nrf2 antioxidant system to protect the nigrostriatal dopaminergic neurons from MPP+ toxicity. Experimental Neurology 2015;263:50-62.
  27. Laing BT, Do K, Matsubara T, Wert DW, Avery MJ, Langdon EM, et al. Voluntary exercise improves hypothalamic and metabolic function in obese mice. Journal of Endocrinology 2016;229(2):109-122.
  28. Olver TD, Laughlin MH, Padilla J. Exercise and vascular insulin sensitivity in skeletal muscle and brain. exercise and sport sciences reviews 2019;47(2):66.
  29. Gusdon AM, Callio J, Distefano G, O'Doherty RM, Goodpaster BH, Coen PM, et al. Exercise increases mitochondrial complex I activity and DRP1 expression in the brains of aged mice. Experimental Gerontology 2017;90:1-13.
  30. Ruegsegger GN, Vanderboom PM, Dasari S, Klaus KA, Kabiraj P, McCarthy CB, et al. Exercise and metformin counteract altered mitochondrial function in the insulin-resistant brain. JCI insight 2019;4(18): e130681.
  31. Lin MY, Cheng XT, Tammineni P, Xie Y, Zhou B, Cai Q, et al. Releasing syntaphilin removes stressed mitochondria from axons independent of mitophagy under pathophysiological conditions. Neuron 2017;94(3):595-610.
  32. Găman MA, Epîngeac ME, Diaconu CC, Găman AM. Evaluation of oxidative stress levels in obesity and diabetes by the free oxygen radical test and free oxygen radical defence assays and correlations with anthropometric and laboratory parameters. WJD 2020;11(5):193.
  33. Thirupathi A, Pinho RA. Effects of reactive oxygen species and interplay of antioxidants during physical exercise in skeletal muscles. Journal of Physiology and Biochemistry 2018;74(3):359-367.
  34. Zhang Z, Liu H, Liu J. Akt activation; A potential strategy to ameliorate insulin resistance. Diabetes Research Clinical Practice 2019;156:107092.
  35. Taheri A, Rohani H, Habibi A. The Effect of Endurance Exercise Training on the Expression of Brain-Derived Neurotrophic Factor (BDNF) and Nerve Growth Factor (NGF) Genes of the Cerebellum in Diabetic Rat. IJDO 2019;11(4):233-240.[Persian]