Spine Research Laboratory, Department of Neurosurgery, University of Michigan Medical School, 1500 E, Medical Center Drive, Ann Arbor, Michigan 48109, USA.
Arthritis Res Ther. 2009;11(6):R172. doi: 10.1186/ar2861. Epub 2009 Nov 13.
Earlier work indicates that the cholesterol-lowering drug, simvastatin, is anabolic to chondrogenic expression of rat intervertebral disc (IVD) cells, which suggests a potential role for simvastatin in IVD regeneration. In this study, we expand on our earlier work to test the effectiveness of simvastatin on disc degeneration utilizing a rat tail disc degeneration model.
30 rats that underwent 21 G needle-puncture at rat tail discs were injected with simvastatin-loaded poly(ethylene glycol)-poly(lactic acid-co-glycolic acid)-poly(ethylene glycol) (PEG-PLGA-PEG) gel (5 mg/ml) or vehicle control at 4 weeks after needle injury. All animals were sacrificed 2 weeks after simvastatin injection. Bone morphogenetic protein-2 (BMP-2), aggrecan, collagen type II, and collagen type I messenger ribonucleic acid (mRNA) expression in the rat nucleus pulposus (NP) were measured by real-time polymerase chain reaction (PCR). In vivo magnetic resonance imaging (MRI) was performed to monitor changes in disc degeneration. Rat discs were also assessed by histology using hematoxylin and eosin (H&E) and safranin O staining. In addition, the NP weight, glycosaminoglycan (sGAG) and DNA content were also measured.
A single dose of simvastatin loaded in thermo-sensitive PEG-PLGA-PEG gel injected into the NP had the trend to increase aggrecan expression and sGAG content, and significantly increased mRNA levels of BMP-2, collagen type II, and the differentiation index (the ratio of collagen type II to collagen type I). The decreased NP weight, T2 intensity, as well as MRI index in the rat tail discs induced by needle puncture were significantly reversed after 2 weeks of simvastatin treatment. In addition, simvastatin treatment also improved histological changes induced by needle puncture.
A single injection of simvastatin loaded in PEG-PLGA-PEG gel into rat tail discs had the potential to retard or regenerate the degenerative disc.
早期的研究表明，降脂药物辛伐他汀能促进大鼠椎间盘中软骨细胞的成骨表达，这表明辛伐他汀在椎间盘再生中可能发挥作用。在这项研究中，我们扩展了早期的工作，利用大鼠尾椎间盘退变模型来测试辛伐他汀对椎间盘退变的效果。
30 只大鼠在尾椎间盘处接受 21G 针穿刺后，在针损伤后 4 周时注射辛伐他汀负载的聚乙二醇-聚乳酸-羟基乙酸共聚物-聚乙二醇（PEG-PLGA-PEG）凝胶（5mg/ml）或载体对照。所有动物在辛伐他汀注射后 2 周处死。采用实时聚合酶链反应（PCR）检测大鼠髓核中骨形态发生蛋白-2（BMP-2）、聚集蛋白聚糖、Ⅱ型胶原和Ⅰ型胶原信使核糖核酸（mRNA）的表达。通过体内磁共振成像（MRI）监测椎间盘退变的变化。还通过苏木精和伊红（H&E）和番红 O 染色对大鼠椎间盘进行组织学评估。此外，还测量了 NP 重量、糖胺聚糖（sGAG）和 DNA 含量。
单次注射辛伐他汀负载在温敏性 PEG-PLGA-PEG 凝胶中，注入 NP 有增加聚集蛋白聚糖表达和 sGAG 含量的趋势，并显著增加 BMP-2、Ⅱ型胶原和分化指数（Ⅱ型胶原与Ⅰ型胶原的比值）的 mRNA 水平。针穿刺引起的 NP 重量、T2 强度和大鼠尾椎间盘的 MRI 指数在辛伐他汀治疗 2 周后显著逆转。此外，辛伐他汀治疗还改善了针穿刺引起的组织学变化。
单次注射辛伐他汀负载在 PEG-PLGA-PEG 凝胶中对大鼠尾椎间盘有延缓或再生退变椎间盘的潜力。
