In vivo experimental intervertebral disc degeneration induced by bleomycin in the rhesus monkey.
In vivo experimental intervertebral disc degeneration induced by bleomycin in the rhesus monkey.
复制标题
博来霉素诱导恒河猴体内实验性椎间盘退变
DOI：
10.1186/1471-2474-15-340
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发表时间：
2014-10-09
影响因子：
2.3
通讯作者：
Liu S
中科院分区：
文献类型：
--
作者：
Wei F;Zhong R;Zhou Z;Wang L;Pan X;Cui S;Zou X;Gao M;Sun H;Chen W;Liu S
近期，针对退行性椎间盘疾病早期干预的生物疗法已被引入并得到发展；然而，一种模拟人类缓慢进展性椎间盘退变的功能性动物模型尚不存在。本研究的目的是建立一种缓慢进展且可重复的椎间盘退变模型。
将10只恒河猴的腰椎椎间盘（L3/4和L5/6）相邻的软骨下骨分别随机注射4ml博来霉素溶液（1.5mg/ml），或每节段注射4ml磷酸盐缓冲盐水（PBS）作为对照。在术后1、3、6、9、12和15个月通过X线摄影和T1ρ磁共振成像研究退变过程。在15个月时进行组织学评分、硫酸化糖胺聚糖（GAGs）分析和实时聚合酶链反应（PCR）。还分析了组织学评分、GAGs和T1ρ值之间的相关性。
结果显示，博来霉素组的髓核（NP）和纤维环（AF）的平均T1ρ值分别在3个月和6个月后显著下降，随后缓慢下降直至15个月。在15个月时，与对照组相比，博来霉素组的组织学评分显著更高，髓核的GAGs显著更低（P＜0.05）。实时PCR结果显示，博来霉素组在mRNA水平上基质金属蛋白酶（MMP）-3、含血小板反应蛋白结构域的解整合素样金属蛋白酶（ADAMTS）-5、肿瘤坏死因子α、白细胞介素-1β、白细胞介素-6表达显著增加，转化生长因子（TGF -β1）以及聚集蛋白聚糖、Ⅱ型胶原、血管性血友病因子（vWF）表达显著降低。斯皮尔曼相关分析显示，髓核的GAGs和T1ρ值之间呈强正相关（r = 0.740，P＜0.01），组织学评分与髓核和纤维环的T1ρ值之间呈显著负相关（r = -0.761，r = -0.729，分别为P＜0.01）。
向恒河猴腰椎椎间盘相邻的软骨下骨注射博来霉素可导致轻度、缓慢进展的椎间盘退变，其模拟了人类椎间盘退变的发病过程。T1ρ磁共振成像是一种评估早期椎间盘退变的有效且无创的技术。
本文的网络版（doi:10.1186/1471 - 2474 - 15 - 340）包含补充材料，可供授权用户使用。
BackgroundRecently, biological therapies for early intervention of degenerative disc disease have been introduced and developed; however, a functional animal model that mimics slowly progressive disc degeneration of humans does not exist. The objective of this study was to establish a slowly progressive and reproducible intervertebral disc (IVD) degeneration model.MethodsThe subchondral bone adjacent to the lumbar IVDs (L3/4 and L5/6) of ten rhesus monkeys was randomly injected with 4 ml bleomycin solution (1.5 mg/ml), or 4 ml phosphate buffer saline (PBS) per segment as control, respectively. The degenerative process was investigated by using radiography and T1ρ MR imaging at 1, 3, 6, 9, 12 and 15 months postoperatively. Histological scoring, Sulfated Glycosaminoglycans (GAGs) analysis and real-time PCR were performed at 15 months. The correlation between histological score, GAGs and T1ρ values were also analyzed.ResultsThe results showed that the mean T1ρ values of nucleus pulposus (NP) and annulus fibrosus (AF) in the bleomycin group significantly decreased after 3 and 6 months respectively, followed by slowly decrease until at 15 months. At 15 months, the histological scores was significantly higher, and the GAGs of NP was significantly lower in the bleomycin group, compared with the control group (P< 0.05). The results of real-time PCR revealed a significant increase in matrix metalloprotease (MMP)-3, A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-5, tumor necrosis factor α, interleukin-1β, interleukin-6 expressions, transforming growth factor (TGF-β1) and marked reduction in aggrecan, type II collagen, von willebrand factor (vWF) expressions at the mRNA levels in the bleomycin group. Spearman correlation analysis showed a strong positive correlation between GAGs and T1ρ values of NP (r =0.740,P< 0.01), and a significant inverse correlation between histological score and T1ρ values of NP and AF (r = -0.761, r = -0.729, respectively,P< 0.01).ConclusionsInjection of bleomycin into the subchondral bone adjacent to the lumbar IVDs of rhesus monkeys can results in mild, slowly progressive disc degeneration, which mimics the onset of human disc degeneration. T1ρ MR imaging is an effective and noninvasive technique for assessment of early stage disc degeneration.
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影响因子：
3
作者：
Duncan AE;Colman RJ;Kramer PA
通讯作者：
Kramer PA
影响因子：
2.8
作者：
Hirata, Hiroaki;Yurube, Takashi;Nishida, Kotaro
通讯作者：
Nishida, Kotaro
影响因子：
3.3
作者：
Cervellati, F.;Cervellati, C.;Valacchi, G.
通讯作者：
Valacchi, G.
DOI：
10.1016/0304-4165(86)90306-5
发表时间：
1986-09-04
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
FARNDALE, RW;BUTTLE, DJ;BARRETT, AJ
通讯作者：
BARRETT, AJ
DOI：
10.1196/annals.1397.069
发表时间：
2007-01-01
期刊：
SIGNAL TRANSDUCTION PATHWAYS, PT D
影响因子：
--
作者：
Bachmeier, Beatrice E.;Nerlich, Andreas G.;Boos, Norbert
通讯作者：
Boos, Norbert