THE ROLE OF NITRIC OXIDE, MATRIX METALLOPTOTEINASE AND TUMOR NECROTIZING FACTOR-α DURING THE PROCESS OF INTERVERTEBRAL DISC DEGENERATION AND REGENERATION

椎间盘退变是椎间盘功能障碍和腰痛的主要原因。许多因素已知影响椎间盘退变。一氧化氮（NO）、基质金属蛋白酶（MMP）和肿瘤坏死因子-α(TNF-α)在椎间盘代谢的多种生理过程中的作用变得明显。我们阐明了NO、MMP和TNF-α在椎间盘代谢中的作用，以及i-NOS抑制剂、MMP抑制剂和TNF-α抑制剂对其产生的控制作用，以防止实验性兔椎间盘退变模型。术后1个月x线片显示椎间盘间隙缩小。组织学上，在变性过程中，红素- o染色减少和纤维环撕裂的产生是明显的。蛋白聚糖和DNA的合成活性也降低。采用夹心酶免疫分析法检测mmp1、3、9、12、13和timp1、2。这些酶在椎间盘退变过程中显著增加，退变兔椎间盘自发产生NO， NO抑制椎间盘内蛋白多糖的合成。我们研究了i-NOS抑制剂（L-LMMA）、MMP抑制剂和TNF-α抑制剂对椎间盘退变过程的影响。NO抑制剂抑制NO的产生和蛋白多糖的合成速率，但对MMP和TNF-α的产生无影响。TNF-α抑制剂抑制TNF-α和MMP的产生，抑制椎间盘退变过程。从这些结果来看，抑制TNF-α和MMP的产生对促进椎间盘再生很重要。

The intervertebral disc degeneration is the major cause of disc dysfunction and low back pain. Many factors are known to influence intervertebral disc degeneration. The role of nitric oxide (NO), matrix metalloproteinase (MMP), and tumor necrotizing factor-α(TNF-α) in a variety of physiological processes of the intervertebral disc metabolism became apparent. We have clarified that the role of NO,MMP and TNF-α in disc metabolism and the effects of i-NOS inhibitor, MMP inhibitor and TNF-α inhibitor that control these production to prevent experimental rabbit disc degeneration model.Radiographs revealed intervertebral disc space narrowing after 1 month after surgery. Histologically, the reduction of Safranin-O staining and production of annulus fibrosus tear during the degeneration process are apparent. The synthetic activities of proteoglycan and DNA were also decreased. MMP 1,3,9,12,13, and TIMP 1 and 2 were determined by sandwich enzyme immunoassay method. These enzymes were increased dramatically in the intervertebral disc degeneration process, and the degenerated rabbit intervertebral disc spontaneously produced NO and NO inhibited proteoglycan synthesis in the disc. We investigated the effect of i-NOS inhibitor (L-LMMA), MMP inhibitor and TNF-α inhibitor on the degenerated process of the disc. NO inhibitor inhibited the NO production and proteoglycan synthesis rate, but had no effect on MMP and TNF-α production. But, TNF-α inhibitor inhibited TNF-α and MMP production, and also inhibited degeneration process of the disc. From these results, it is important to inhibit TNF-α and MMP production to promote intervertebral disc regeneration.