Zhang Liang, Niu Tao, Yang Shang-You, Lu Zhenhua, Chen Bohua
Surgical Department, Medical College of Qingdao University, Shandong, People's Republic of China.
Spine (Phila Pa 1976). 2008 Feb 15;33(4):422-7. doi: 10.1097/BRS.0b013e318163e036.
Intervertebral discs surgically obtained from 60 herniated patients and 5 normal individuals were examined to correlate the regional distribution of DR4-receptor and apoptosis.
To explore the role of a tumor necrosis factor superfamily member DR4 and the TRAIL/DR4 mediated apoptosis in the human lumbar intervertebral disc.
The pathogenesis of lumbar degenerative intervertebral discs remains not completely understood. In herniated lumbar disc tissues, increased apoptosis and higher expression of Fas/Fas ligand and caspase-3 have been reported, suggesting a pivotal role of apoptotic mechanisms in intervertebral disc degeneration. However, it is not clear that apoptosis mediators such as TRAIL and Death Receptor 4 (DR4), which often represent different apoptosis signal pathways, contribute to the apoptosis process during the development of the degenerated intervertebral discs.
Apoptosis was determined by poly(ADP-ribose) polymerase (PARP) p85 immunohistochemistry. Expression of DR4 was revealed by immunohistochemistry analysis. Statistical difference among groups was analyzed using one-way ANOVA with LSD post hoc multiple comparisons and the bivariate correlations.
Apoptotic cells were detected in the nucleus pulposus and anulus fibrosus of all samples. However, the number of apoptotic cells was significantly higher in the nucleus compared with the anulus. Further, there were significantly more apoptotic cells in the herniated discs compared with the normal discs. Within herniated discs, a remarkably higher percentage of positive staining cells were detected in the uncontained discs than the contained ones. Strong expression of DR4 was detected in all samples of degenerative herniated discs, whereasmuch weaker expression was sporadically identified in normal discs. In addition, the prevalence of apoptosis positively correlated with the severity of disc degeneration.
The concomitant increase of DR4 expression in the regions of heavy apoptotic cell aggregation suggests that TRAIL/DR4-mediated pathway may play an important role in the apoptosis in herniated discs.
对从60例椎间盘突出患者和5例正常人手术获取的椎间盘进行检查，以关联DR4受体的区域分布与细胞凋亡情况。
探讨肿瘤坏死因子超家族成员DR4以及TRAIL/DR4介导的细胞凋亡在人腰椎椎间盘中的作用。
腰椎间盘退变的发病机制尚未完全明了。据报道，在腰椎间盘突出症组织中，细胞凋亡增加，Fas/Fas配体和半胱天冬酶-3的表达更高，提示凋亡机制在椎间盘退变中起关键作用。然而，尚不清楚诸如TRAIL和死亡受体4（DR4）等凋亡介质，它们通常代表不同的凋亡信号通路，是否在退变椎间盘的发育过程中的细胞凋亡进程中发挥作用。
通过聚（ADP-核糖）聚合酶（PARP）p85免疫组织化学法测定细胞凋亡情况。通过免疫组织化学分析揭示DR4的表达。使用单因素方差分析及LSD事后多重比较和双变量相关性分析各组间的统计学差异。
在所有样本的髓核和纤维环中均检测到凋亡细胞。然而，髓核中的凋亡细胞数量明显高于纤维环。此外，与正常椎间盘相比，突出椎间盘中的凋亡细胞明显更多。在突出椎间盘中，未包含型椎间盘的阳性染色细胞百分比明显高于包含型椎间盘。在所有退变突出椎间盘样本中均检测到DR4的强表达，而在正常椎间盘中偶尔能发现较弱的表达。此外，细胞凋亡的发生率与椎间盘退变的严重程度呈正相关。
在凋亡细胞大量聚集区域DR4表达的同时增加表明，TRAIL/DR4介导的途径可能在突出椎间盘中的细胞凋亡中起重要作用。
