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大鼠坐骨神经横断及修复后发生的退行性和再生现象的研究:乙酰-L-肉碱的作用

Studies on the degenerative and regenerative phenomena occurring after transection and repair of the sciatic nerve in rats: effects of acetyl-L-carnitine.

作者信息

Fernandez E, Pallini R, Gangitano C, Del Fa A, Olivieri-Sangiacomo C, Sbriccoli A, Ricoy J, Rossi G F

机构信息

Institute of Neurosurgery, Catholic University School of Medicine, Rome, Italy.

出版信息

Int J Clin Pharmacol Res. 1990;10(1-2):85-99.

PMID:2387666
Abstract

The effects of acetyl-L-carnitine on some degenerative and regenerative phenomena following sciatic nerve transection in rats, were studied. In Experiment 1, acetyl-L-carnitine was administered intraperitoneally at the dose of 50 mg/kg/day for 28 and 56 days following transection and microsurgical repair of the sciatic nerve. On day 56, the acetyl-L-carnitine-treated rats showed a significantly (p less than 0.05) better motor recovery ("clinical assessment") of the peroneal component of the sciatic nerve than the control rats. Twenty-eight days after nerve repair, the acetyl-L-carnitine-treated rats showed a significantly higher (p less than 0.05) number of myelinated axons in the postlesional nerve stump than control rats. Finally, the treated rats had a significantly lower (p less than 0.05) presence of atrophic fibres in the extensor digitorum longus muscle. In Experiment 2 the sciatic nerve was cut. To prevent spontaneous regeneration, a metallic clip was applied to the distal nerve stump and then the nerve stumps were positioned in different anatomical compartments. After surgery, a group of rats was treated with acetyl-L-carnitine dissolved in the drinking water (75 mg/kg/day). Another group of rats received normal water and served as the control group. Three, 6, 9, 12 and 18 months postoperatively, in the rats of both groups, the proximal sciatic nerve stump was injected with horseradish peroxidase to label the spinal cord neurons of the sciatic nerve nucleus. While in untreated rats the number of horseradish peroxidase-labelled neurons decreased with the increase in denervation time, in acetyl-L-carnitine-treated rats the number of horseradish peroxidase-labelled neurons remained stable for as long as 12 months of denervation and decreased only after 18 months of denervation. Furthermore, acetyl-L-carnitine-treated rats showed a significantly higher (p less than 0.05) number of horseradish peroxidase-labelled neurons with respect to untreated rats both after 9 and 12 months of denervation. In Experiment 3, the sciatic nerve was cut and then repaired after periods of 3, 6, 9, 12, and 18 months. Four months after nerve repair, the sciatic nerve was again cut and the proximal nerve stump was injected with horseradish peroxidase to label the spinal cord neurons of the sciatic nerve nucleus. Both acetyl-L-carnitine-treated and untreated rats showed a tendency to have an increased number of horseradish peroxidase-labelled neurons with respect to intact rats of correspondent ages.(ABSTRACT TRUNCATED AT 400 WORDS)

摘要

研究了乙酰 - L - 肉碱对大鼠坐骨神经横断后一些退行性和再生性现象的影响。在实验1中,坐骨神经横断并显微外科修复后,以50 mg/kg/天的剂量腹腔注射乙酰 - L - 肉碱,持续28天和56天。在第56天,与对照大鼠相比,经乙酰 - L - 肉碱处理的大鼠坐骨神经腓总神经成分的运动恢复(“临床评估”)明显更好(p < 0.05)。神经修复28天后,经乙酰 - L - 肉碱处理的大鼠损伤后神经残端中有髓轴突数量明显多于对照大鼠(p < 0.05)。最后,处理组大鼠趾长伸肌中萎缩纤维的数量明显更少(p < 0.05)。在实验2中,切断坐骨神经。为防止自发再生,在远端神经残端施加金属夹,然后将神经残端置于不同的解剖部位。手术后,一组大鼠饮用溶解有乙酰 - L - 肉碱的水(75 mg/kg/天)。另一组大鼠饮用正常水作为对照组。术后3、6、9、12和18个月,对两组大鼠的坐骨神经近端残端注射辣根过氧化物酶,以标记坐骨神经核的脊髓神经元。在未处理的大鼠中,随着去神经时间的增加,辣根过氧化物酶标记的神经元数量减少,而在经乙酰 - L - 肉碱处理的大鼠中,辣根过氧化物酶标记的神经元数量在去神经12个月内保持稳定,仅在去神经18个月后减少。此外,在去神经9个月和12个月后,经乙酰 - L - 肉碱处理的大鼠辣根过氧化物酶标记的神经元数量明显多于未处理的大鼠(p < 0.05)。在实验3中,切断坐骨神经,然后在3、6、9、12和18个月后进行修复。神经修复4个月后,再次切断坐骨神经,并向近端神经残端注射辣根过氧化物酶,以标记坐骨神经核的脊髓神经元。与相应年龄的完整大鼠相比,经乙酰 - L - 肉碱处理和未处理的大鼠辣根过氧化物酶标记的神经元数量均有增加的趋势。(摘要截选至400字)

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