Zhang Huina, La Marca Frank, Hollister Scott J, Goldstein Steven A, Lin Chia-Ying
Spine Research Laboratory, Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, Michigan 48109-2200, USA.
J Neurosurg Spine. 2009 Jun;10(6):522-30. doi: 10.3171/2009.2.SPINE08925.
The goal in this study was to develop a convenient, less-invasive animal model to monitor progression of intervertebral disc (IVD) degeneration for future testing of new treatments for disc degeneration.
Level 5/6 and 7/8 IVDs of rat caudal spine were stabbed laterally with 18- or 21-gauge hypodermic needles to a depth of 5 mm from the subcutaneous surface with the aid of fluoroscopy. In vivo MR imaging studies were performed at 4, 8, and 12 weeks postsurgery to monitor progression of IVD degeneration. Histological analysis including H & E and safranin O staining, and immunohistochemical studies of collagen type II and bone morphogenetic protein receptor type II (BMPRII) were assessed at 12 weeks postsurgery.
The 18- and 21-gauge needle-stabbed discs illustrated decreases in both the T2 density and MR imaging index starting at 4 weeks, with no evidence of spontaneous recovery by 12 weeks. Histological staining demonstrated a decreased nucleus pulposus (NP) area, and the NP-anulus fibrosus border became unclear during the progression of disc degeneration. Similar patterns of degenerative signs were also shown in both safranin O- and collagen type II-stained sections. The BMPRII immunohistochemical analysis of stabbed discs demonstrated an increase in BMPRII expression in the remaining NP cells and became stronger in anulus fibrosus with the severity of disc degeneration.
After introducing an 18- or 21-gauge needle into the NP area of discs in the rat tail, the stabbed disc showed signs of degeneration in terms of MR imaging and histological outcome measurements. Changes in BMPRII expression in this animal model provide an insight for the effectiveness of delivering BMPs into the region responsible for chondrogenesis for disc repair. This convenient, less-invasive, reproducible, and cost-effective model may be a useful choice for testing novel treatments for disc degeneration.
本研究的目标是建立一种方便、侵入性较小的动物模型，以监测椎间盘（IVD）退变的进展，用于未来椎间盘退变新治疗方法的测试。
借助荧光透视，用18号或21号皮下注射针在大鼠尾椎的第5/6和7/8椎间盘侧面刺入，从皮下表面刺入深度为5毫米。在术后4周、8周和12周进行体内磁共振成像研究，以监测IVD退变的进展。在术后12周评估组织学分析，包括苏木精和伊红（H&E）染色、番红O染色，以及II型胶原蛋白和骨形态发生蛋白受体II型（BMPRII）的免疫组织化学研究。
18号和21号针刺的椎间盘从4周开始T2密度和磁共振成像指数均下降，到12周时无自发恢复迹象。组织学染色显示髓核（NP）面积减小，在椎间盘退变过程中NP与纤维环边界变得不清楚。在番红O染色和II型胶原蛋白染色切片中也显示出类似的退变迹象模式。针刺椎间盘的BMPRII免疫组织化学分析显示，剩余NP细胞中BMPRII表达增加，并随着椎间盘退变的严重程度在纤维环中变得更强。
将18号或21号针插入大鼠尾部椎间盘的NP区域后，针刺的椎间盘在磁共振成像和组织学结果测量方面显示出退变迹象。该动物模型中BMPRII表达的变化为将骨形态发生蛋白（BMPs）输送到负责椎间盘修复软骨形成的区域的有效性提供了见解。这种方便、侵入性较小、可重复且经济高效的模型可能是测试椎间盘退变新治疗方法的有用选择。
