Department of Neurosurgery, Taichung Veterans General Hospital, Taichung, Taiwan.
Neurosurgery. 2010 Aug;67(2):376-88; discussion 388-9. doi: 10.1227/01.NEU.0000371729.47895.A0.
Statins have therapeutic benefits for the management of several disorders. A short-term course of a high-dose statin pretreatment has demonstrated neuroprotective effects against neurological diseases. However, the molecular basis underlying the neuroprotective action of statins remains unclear.
We investigated whether a short-term course of high-dose atorvastatin pretreatment has beneficial effects in protecting sciatic nerve from crush injury.
Atorvastatin (5 mg/kg) or saline was given orally to Sprague-Dawley rats for 7 days before injury. The rats were subjected to crush injury in the left sciatic nerve with a vessel clamp. Biochemical, functional, electrophysiological, and morphological alterations occurring during injury-induced degeneration/regeneration were examined.
Atorvastatin improved injury-induced neurobehavioral/electrophysiological changes and axonal loss. Damage-associated alterations, including structural disruption, oxidative stress, inflammation, and apoptosis, were attenuated by atorvastatin. After injury, regeneration-associated genes, including growth-associated protein-43, myelin basic protein, ciliary neurotrophic factor, and collagen, were upregulated by atorvastatin. The suppression of extracellular signal-regulated kinase, AKT, signal transducer and activators of transcription-1, and necrosis factor-kappaB and the elevated activation of c-Jun N-terminal kinase, Smad2/3, and activating protein-1 were associated with the neuroprotective action of atorvastatin.
These findings suggest that a short-term course of high-dose atorvastatin pretreatment can protect against sciatic nerve crush injury through modifying intracellular or extracellular environments, making it favorable for regeneration.
他汀类药物对多种疾病的治疗有好处。短期大剂量他汀预处理已显示出对神经疾病的神经保护作用。然而，他汀类药物的神经保护作用的分子基础仍不清楚。
我们研究了短期大剂量阿托伐他汀预处理是否对保护坐骨神经免受挤压损伤有有益作用。
阿托伐他汀（5mg/kg）或生理盐水在损伤前口服给予 Sprague-Dawley 大鼠 7 天。用血管夹对左侧坐骨神经进行挤压损伤。检查损伤诱导的退化/再生过程中发生的生化、功能、电生理和形态改变。
阿托伐他汀改善了损伤引起的神经行为/电生理变化和轴突丢失。阿托伐他汀减轻了损伤相关的改变，包括结构破坏、氧化应激、炎症和细胞凋亡。损伤后，再生相关基因，包括生长相关蛋白-43、髓鞘碱性蛋白、睫状神经营养因子和胶原蛋白，被阿托伐他汀上调。细胞外信号调节激酶、AKT、信号转导和转录激活因子 1 和肿瘤坏死因子-κB 的抑制以及 c-Jun N 末端激酶、Smad2/3 和激活蛋白-1 的激活与阿托伐他汀的神经保护作用有关。
这些发现表明，短期大剂量阿托伐他汀预处理可以通过改变细胞内或细胞外环境来保护坐骨神经免受挤压损伤，有利于再生。
