Understanding Vibration Injury

描述(申请人提供)：在美国，数百万工人暴露在机械和电动工具的振动中。长期暴露在过度的手传振动中会导致虚弱，通常是永久性的血管、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，以便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在危险振动中的工人的健康、安全和福利。采用大鼠尾振动急、慢性振动性疾病模型，研究大鼠肌肉骨骼、血管和神经系统的原发病变(S)、疾病进展和不可逆性损伤。这4个目的是：1)证明振动的短期和长期效应涉及内皮细胞的丧失和血管内皮细胞的增殖和生长，进而导致动脉血管腔闭塞，导致血流受阻，并确定特定细胞类型的损伤敏感性是否与频率和加速度有关；2)证明振动导致周围神经进行性破坏，导致神经传导受损和轴浆逆行运输受损，并确定损伤敏感性是否与频率和加速度相关；3)用血清免疫分析和神经、血管和骨骼肌细胞数量的酶活性分析与细胞类型特异性、结构性损伤相关；振动损伤后释放到血液中的蛋白质，并开发一种振动损伤的微创监测手段，以及4)在长期振动停止后1、2和3个月表征血流严重受阻和神经传导受抑时的动脉和神经的结构状态。这些研究的结果将进一步加深对振动病发病机制的理解，并为新的监测、治疗和预防策略提供见解。

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.