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椎间盘退变疾病的体内模型。

An in vivo model of degenerative disc disease.

作者信息

Norcross Jason P, Lester Gayle E, Weinhold Paul, Dahners Laurence E

机构信息

Department of Orthopaedic Surgery, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.

出版信息

J Orthop Res. 2003 Jan;21(1):183-8. doi: 10.1016/S0736-0266(02)00098-0.

Abstract

Although the precise etiology of low back pain is disputed, degeneration of the intervertebral disc is believed to play an important role. Many animal models have been described which reproduce the changes found in degenerative disc disease, but none allow for efficient, large-scale testing of purported therapeutic agents. The purpose of this study was to develop a simple animal model resembling degenerative disc disease using the intervertebral discs found in the tails of rats. The proximal two intervertebral discs in the tails of 20 rats were injected with either chondroitinase ABC or control (phosphate buffered saline, PBS). The tails were harvested at 2 weeks, and measurements were made of intervertebral disc height (measured radiographically and histologically), biomechanics (stiffness, hysteresis, and residual deformation), and histologic appearance. Treatment with chondroitinase ABC resulted in a significant loss in intervertebral disc height (radiographic intervertebral disc height, p=0.001; histologic intervertebral disc height, p<0.001) and significant increases in all biomechanical parameters (stiffness, p<0.001; hysteresis, p=0.006; residual deformation, p=0.004) compared to PBS controls. Intervertebral discs treated with chondroitinase ABC had significantly lower histologic grades for each grading category (nucleus pulposus (NP), annulus fibrosus, and proteoglycan staining) compared to controls. The results of injury with chondroitinase ABC were similar to the findings in degenerative disc disease: reduced intervertebral disc height, diminished proteoglycan content, loss of NP cells, and increased stiffness of the disc. Thus, the model appears to be a reasonable tool for the preliminary in vivo evaluation of proposed treatments for degenerative disc disease.

摘要

尽管下腰痛的确切病因存在争议,但椎间盘退变被认为起着重要作用。已经描述了许多动物模型,这些模型再现了退行性椎间盘疾病中发现的变化,但没有一个能允许对所谓的治疗药物进行高效、大规模的测试。本研究的目的是利用大鼠尾部的椎间盘开发一种类似于退行性椎间盘疾病的简单动物模型。给20只大鼠尾部的近端两个椎间盘注射软骨素酶ABC或对照物(磷酸盐缓冲盐水,PBS)。在2周时收获尾部,并测量椎间盘高度(通过放射学和组织学测量)、生物力学(刚度、滞后和残余变形)以及组织学外观。与PBS对照组相比,用软骨素酶ABC治疗导致椎间盘高度显著降低(放射学椎间盘高度,p = 0.001;组织学椎间盘高度,p < 0.001),并且所有生物力学参数均显著增加(刚度,p < 0.001;滞后,p = 0.006;残余变形,p = 0.004)。与对照组相比,用软骨素酶ABC处理的椎间盘在每个分级类别(髓核(NP)、纤维环和蛋白聚糖染色)中的组织学分级显著更低。软骨素酶ABC损伤的结果与退行性椎间盘疾病的发现相似:椎间盘高度降低、蛋白聚糖含量减少、NP细胞丢失以及椎间盘刚度增加。因此,该模型似乎是对退行性椎间盘疾病拟议治疗方法进行初步体内评估的合理工具。

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