Understanding Vibration Injury

描述（由申请人提供）：在美国，数百万工人暴露在机械和动力工具的振动中。长时间暴露在过度的，手传递的振动会导致衰弱，往往是永久性的，血管，神经和肌肉骨骼问题。我们的长期目标是在细胞和分子水平上了解振动损伤的机制，以确定监测和预防手臂振动综合征的策略。这些研究有助于改善暴露于有害振动的工人的健康、安全和福利。利用大鼠尾部振动、急性和慢性振动疾病模型来表征肌肉骨骼、血管和神经系统的原发性病变、疾病进展和不可逆损伤。4个目的是：1）证明振动的短期和长期效应涉及内皮细胞损失和平滑肌细胞的增殖和生长，其进展为动脉血管腔的闭塞，导致血流受阻，并确定特定细胞类型的损伤易感性是否依赖于频率和加速度，2）证明振动产生周围神经的进行性破坏，这导致受损的神经传导和受损的逆行轴浆运输，并确定损伤易感性是否是频率和加速度依赖性的，3）将细胞类型特异性，用血清免疫测定法和酶活性测定法对振动损伤后释放到血液中的神经、血管和骨骼肌细胞特异性蛋白质的量进行结构损伤，并开发一种振动损伤的微创监测方法，以及4）在停止长期振动后1、2和3个月时表征，动脉和神经的结构状态，当血液流动严重受阻和神经传导受到抑制时。这些研究的结果将进一步了解振动疾病的发病机制，并提供新的监测，治疗和预防策略的见解。

DESCRIPTION (provided by applicant): In America, millions of workers are exposed to vibration from machinery and powered tools. Prolonged exposure to excessive, hand transmitted vibration causes debilitating, often permanent, vascular, neural and musculoskeletal problems. Our long-term goal is to understand the mechanism of vibration injury at the cellular and molecular levels in order to define strategies for monitoring and preventing hand arm vibration syndrome. These studies help to improve the health, safety and welfare of workers exposed to hazardous vibration. A rat tail vibration, model of acute and chronic vibration disease is utilized for characterizing the primary lesion(s), disease progression and irreversible injury of the musculoskeletal, vascular and neural systems. The 4 aims are 1) to demonstrate that the short and long duration effects of vibration involve endothelial cell loss and the proliferation and in growth of smooth muscles cells, which progress to occlusion of the arterial blood vessel lumen resulting in impeded blood flow and to ascertain whether injury susceptibility of specific cell types is frequency and acceleration dependent, 2) to demonstrate that vibration produces progressive disruptions of peripheral nerves, which result in compromised nerve conduction and impaired retrograde axoplasmic transport and to ascertain whether injury susceptibility is frequency and acceleration dependent, 3) to correlate cell type specific, structural damage with serum immunoassays and enzyme activity assays of the amounts of neural, vascular and skeletal muscle cell specific, proteins released into the blood following vibration injury and to develop a means of minimally invasive monitoring of vibration injury, and 4) to characterize at 1, 2 and 3 months after stopping long term vibration, the structural states of arteries and nerves, when blood flow is severely obstructed and nerve conduction is depressed. The results of these studies will further the understanding of the pathogenesis of vibration disease and provide insights into novel monitoring, treatment and preventative strategies.