目的:我们研究了L-肉碱(LC)对Cuprizone(Cup)脱髓鞘大鼠模型的影响及其可能的潜在机制。
方法:将30只雄性SD大鼠随机分为3组:正常对照组;其中Cup以450mg/kg/天的剂量通过胃灌胃给药5周;和Cup+LC组,它接受了与杯子组相同剂量的杯子,除了大鼠另外用LC100mg/kg/天口服治疗5周。测量孤立的坐骨神经的神经传导(NCV);然后,分离坐骨神经进行H&E染色和电镜检查。髓鞘碱性蛋白(MBP)的表达,IL-1β,p53,iNOS,通过免疫组织化学在分离的神经中检测到和NF-kB。还进行了PCR测定以检测抗氧化基因Nrf2和HO-1的表达。此外,ELISA法检测IL-17水平。
结果:与正常大鼠相比,Cup组的NCV显着降低(p<0.001),LC组显著改善(p<0.001)。EM和组织病理学检查显示坐骨神经纤维明显脱髓鞘和恶化,LC组有显著改善。IL-17的水平以及IL-1β的表达,p53,iNOS,NF-κB显著增加,坐骨神经中MBP的表达显着降低(p<0.01),LC处理显著改善了所研究的参数(p<0.01)。
结论:本研究证明了LC在Cup诱导的脱髓鞘大鼠模型中的神经保护作用。这种作用可能是由于其抗炎和抗氧化作用。
OBJECTIVE: We investigated the effect of L-carnitine (LC) on cuprizone (Cup)
demyelinating rat model and its possible underlying mechanisms.
METHODS: Thirty male Sprague-Dawley (SD) rats were randomly allocated to three groups: the normal control group; the Cup group, in which Cup was administrated at a dose of 450 mg/kg per day orally via gastric gavage for 5 weeks; and the Cup + LC group, which received the same dose of Cup as the Cup group, except that the rats were treated additionally with LC 100 mg/kg/day orally for 5 weeks. The nerve conduction (NCV) in isolated sciatic nerves was measured; then, the sciatic nerves were isolated for H&E staining and electron microscope examination. The expression of myelin basic protein (MBP), IL-1β, p53, iNOS, and NF-KB by immunohistochemistry was detected in the isolated nerves. A PCR assay was also performed to detect the expression of antioxidant genes Nrf2 and HO-1. In addition, the level of IL-17 was measured by ELISA.
RESULTS: There was a significant reduction in NCV in the Cup group compared to normal rats (p < 0.001), which was significantly improved in the LC group (p < 0.001). EM and histopathological examination revealed significant demyelination and deterioration of the sciatic nerve fibers, with significant improvement in the LC group. The level of IL-17 as well as the expression of IL-1β, p53, iNOS, and NF-KB were significantly increased, with significant reduction expression of MBP in the sciatic nerves (p < 0.01), and LC treatment significantly improved the studied parameters (p < 0.01).
CONCLUSIONS: The current study demonstrates a neuroprotective effect of LC in a Cup-induced
demyelinating rat model. This effect might be due to its anti-inflammatory and antioxidant actions.