肌肽可改善大鼠坐骨神经挤压伤后的功能恢复和结构再生。
Carnosine improves functional recovery and structural regeneration after sciatic nerve crush injury in rats.
机构信息
Division of Pathology, Department of Pathobiology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran.
Division of Pathology, Department of Pathobiology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran.
出版信息
Life Sci. 2018 Dec 15;215:22-30. doi: 10.1016/j.lfs.2018.10.043. Epub 2018 Nov 1.
AIMS
Peripheral nerve injury represents a substantial clinical problem with insufficient or unsatisfactory treatment options. Current researches have extensively focused on the new approaches for the treatment of peripheral nerve injuries. Carnosine is a naturally occurring pleotropic dipeptide and has many biological functions such as antioxidant property. In the present study, we examined the regenerative ability of carnosine after sciatic nerve crush injury using behavioral, biochemical, histological and ultrastructural evaluations.
MATERIALS AND METHODS
Seventy-two rats were divided into six groups including control, sham, crush and carnosine (10, 20 and 40 mg/kg) groups. Crush injury in left sciatic nerve was induced by a small haemostatic forceps. Carnosine was administered for 15 consecutive days after induction of crush injury. Sciatic functional index (SFI) was recorded weekly. Histopathological and ultrastructural evaluations were made using light and electron microscopes, respectively. Sciatic nerve tissue malondialdehyde (MDA), superoxide dismutase (SOD) and tumor necrosis factor-alpha (TNF-α) levels were measured. Gastrocnemius muscle weight was determined.
KEY FINDINGS
Carnosine at the doses of 20 and 40 mg/kg accelerated SFI recovery. Wallerian degeneration severity and myelinated fibers density, myelin sheath thickness and diameter as well as ultrastructural changes of myelinated axons were improved. It also recovered nerve tissue biochemical (MDA, SOD and TNF-α) changes induced by crush injury. Muscle weight ratio was reached to near normal values. Our results suggest a regenerative effect of carnosine. Inhibition of oxidative stress and inflammatory pathways, along with provocation of myelination and prevention of muscular atrophy might be involved in this effect of carnosine.
SIGNIFICANCE
Carnosine treatment might be considered as a therapeutic agent for peripheral nerve regeneration and its functional recovery.
目的
周围神经损伤是一个严重的临床问题,目前的治疗选择效果有限或不尽如人意。目前的研究广泛集中在治疗周围神经损伤的新方法上。肌肽是一种天然存在的多功能二肽,具有抗氧化等多种生物学功能。在本研究中,我们通过行为学、生物化学、组织学和超微结构评估,研究了肌肽在坐骨神经挤压伤后的再生能力。
材料和方法
72 只大鼠分为对照组、假手术组、挤压组和肌肽(10、20 和 40mg/kg)组。用小型止血钳诱导左侧坐骨神经挤压伤。在诱导挤压伤后,连续 15 天给予肌肽。每周记录坐骨神经功能指数(SFI)。使用光镜和电子显微镜分别进行组织病理学和超微结构评估。测量坐骨神经组织丙二醛(MDA)、超氧化物歧化酶(SOD)和肿瘤坏死因子-α(TNF-α)水平。测定比目鱼肌重量。
主要发现
肌肽 20 和 40mg/kg 剂量可加速 SFI 恢复。Wallerian 变性严重程度和有髓神经纤维密度、髓鞘厚度和直径以及有髓轴突的超微结构变化得到改善。它还恢复了挤压伤引起的神经组织生化(MDA、SOD 和 TNF-α)变化。肌肉重量比接近正常水平。我们的结果表明肌肽具有再生作用。抑制氧化应激和炎症途径,同时刺激髓鞘形成和防止肌肉萎缩可能参与了肌肽的这种作用。
意义
肌肽治疗可能被认为是周围神经再生及其功能恢复的治疗剂。