Simvastatin对大鼠坐骨神经钳夹损伤后脊髓小胶质细胞反应性及神经修复作用的影响

发布时间：2018-06-06 07:54

本文选题：Simvastatin + 周围神经钳夹损伤　；参考：《大连医科大学》2006年硕士论文

【摘要】： 研究背景及目的:他汀类药物(Statins)是3-羟-3-甲基戊二酰辅酶A(3-hydroxy-3-methylglutaryl coenzyme A,HMG-CoA)还原酶抑制剂,为当前临床应用最广泛的调脂药物。近年来研究发现,该类药物通过抑制小GTP结合蛋白Rac、Ras和Rho等发挥其非降血脂的多效性效应,在脑中风、老年性痴呆、新生动物缺血缺氧性脑损伤和多发性硬化等神经系统疾病中发挥了重要的神经保护作用。最近临床前研究显示调控Rho GTP酶(Rac,Rho,Cdc42,Tc10)的作用有可能促进神经损伤后功能的恢复。因此提示Statins在神经系统另一发病率很高的疾病—周围神经损伤中有可能通过其非降血脂的多效性效应促进神经修复和再生。近年来的研究显示,周围神经损伤后由受损神经元介导的小胶质细胞的激活促进损伤运动神经元的修复,是神经再生过程的重要组成部分。因此本实验研究的主要目的在于探讨周围神经损伤与修复过程中脊髓小胶质细胞的反应性,并阐明Simvastatin对坐骨神经损伤的修复和再生作用以及可能的作用机制。实验材料与方法:实验选用健康成年雌性Sprague-Dawley大鼠60只为研究对象,随机分为3组:模型组,Simvastatin干预组和假手术组。建立坐骨神经钳夹损伤模型,给予Simvastatin(20mg/kg/d)灌胃治疗,每天一次,连续灌胃两周。于术后一个月以内进行行为学观察及趾展功能指数测定,2w和4w时进行神经传导速度以及复合肌肉动作电位电检测。4w时甲苯胺蓝染色记数有髓神经纤维数量与髓鞘厚度,电镜观察再生神经
[Abstract]:Research background and purpose: the statin drug (Statins) is the 3- hydroxy-3- methyl amyl two acyl coenzyme A (3-hydroxy-3-methylglutaryl coenzyme A, HMG-CoA) reductase inhibitor, which is the most widely used lipid regulating drug at present. In recent years, it has been found that this kind of drug exerts its non hyperlipidemia by inhibiting the small GTP binding protein Rac, Ras and Rho. Effect effects play an important neuroprotective role in cerebral apoplexy, Alzheimer's disease, neonatal hypoxic-ischemic brain damage and multiple sclerosis. Recent preclinical studies have shown that the role of regulating Rho GTP enzyme (Rac, Rho, Cdc42, Tc10) may promote the recovery of function after nerve injury. Therefore, Statins is suggested. In recent years, the activation of microglia mediated by damaged neurons promotes the repair of injured motor neurons, which is the process of nerve regeneration. The main purpose of this study is to explore the reactivity of spinal microglia in the process of peripheral nerve injury and repair, and to elucidate the effect of Simvastatin on the repair and regeneration of sciatic nerve injury and the possible mechanism of action.
Experimental materials and methods: 60 healthy adult female Sprague-Dawley rats were selected as the subjects. They were randomly divided into 3 groups: model group, Simvastatin intervention group and sham operation group. The sciatic nerve clamp injury model was established and Simvastatin (20mg/kg/d) was given to the stomach for two weeks. The number of myelinated nerve fibers and the thickness of myelin sheath were recorded at 2W and 4W at 2W and 4W.
【学位授予单位】：大连医科大学
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R361

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