Wang Jing, Tang Tiansi, Yang Huilin, Yao Xiaoshen, Chen Liang, Liu Wei, Li Tao
Department of Orthopedic Surgery, First Affiliated Hospital of Suzhou University, Suzhou, China.
J Neurosurg Spine. 2007 May;6(5):425-30. doi: 10.3171/spi.2007.6.5.425.
The nucleus pulposus has been reported to be an immunologically privileged site. The expression of Fas ligand (FasL) on normal and herniated lumbar disc cells has been reported. The relationship between a physiological barrier and the role of FasL has not yet been addressed. To clarify this relationship and to investigate a possible pathogenesis of intervertebral disc degeneration (IDD), the expression of Fas and FasL (a mean apoptosis index) on normal and stabbed-disc cells was examined in a rabbit model of IDD.
Using defined needle gauges and depths, the anular puncture model of IDD was established in rabbits. The normal and stabbed discs were harvested at 3, 6, and 10 weeks after surgery. Immunohistochemical staining of these discs for Fas and FasL was performed using standard procedures. The mean apoptosis indices of the disc cells were determined using flow cytometry analysis. The nucleus pulposus cells from the normal discs exhibited relatively weak immunopositivity, whereas the nucleus pulposus cells from the stabbed discs exhibited strong immunopositivity. There was a significant difference (p < 0.001) in the percentage of FasL-positive nucleus pulposus cells between the normal discs and the stabbed discs. The mean apoptosis indices of the stabbed-disc cells at 3, 6, and 10 weeks poststab were significantly higher than those in normal disc cells (p < 0.001, 0.002, and 0.006, respectively). There was a significant correlation between the degree of FasL-positive expression and the degree of Fas-positive expression of the nucleus pulposus cells poststab (r = 0.571, p = 0.0036).
These observations indicate that the nucleus pulposus is an immunologically privileged site. This immunological privilege is maintained by FasL and the physiological barrier together. When the physiological barrier was damaged (by stabbing the disc), the role of FasL changed, and FasL was coexpressed with Fas to induce apoptosis of disc cells. These results indicate that an autoimmune reaction may be a possible pathogenesis of IDD.
据报道，髓核是一个免疫赦免部位。已有研究报道了正常和突出腰椎间盘细胞上Fas配体（FasL）的表达情况。然而，生理屏障与FasL作用之间的关系尚未得到探讨。为了阐明这种关系并研究椎间盘退变（IDD）可能的发病机制，我们在兔IDD模型中检测了正常和针刺椎间盘细胞上Fas和FasL的表达（平均凋亡指数）。
使用特定规格的针和深度，在兔身上建立IDD的纤维环穿刺模型。术后3、6和10周收集正常和针刺椎间盘。采用标准程序对这些椎间盘进行Fas和FasL的免疫组织化学染色。使用流式细胞术分析确定椎间盘细胞的平均凋亡指数。正常椎间盘的髓核细胞显示出相对较弱的免疫阳性，而针刺椎间盘的髓核细胞显示出较强的免疫阳性。正常椎间盘和针刺椎间盘之间FasL阳性髓核细胞的百分比存在显著差异（p < 0.001）。针刺后3、6和10周针刺椎间盘细胞的平均凋亡指数显著高于正常椎间盘细胞（分别为p < 0.001、0.002和0.006）。针刺后髓核细胞FasL阳性表达程度与Fas阳性表达程度之间存在显著相关性（r = 0.571，p = 0.0036）。
这些观察结果表明，髓核是一个免疫赦免部位。这种免疫赦免是由FasL和生理屏障共同维持的。当生理屏障受损（通过针刺椎间盘）时，FasL的作用发生改变，FasL与Fas共同表达以诱导椎间盘细胞凋亡。这些结果表明，自身免疫反应可能是IDD的一种发病机制。
