NGF及其受体TrkA、P75在腰椎间盘突出症患者椎间盘中表达及与腰腿痛关系

Nerve growth factor,tyrosine kinase A and p75 neurotrophin receptor expression in the human herniated intervertebral disc and effect of NGF on clinical symptoms

目的研究椎间盘突出症患者椎间盘中NGF及其受体TrkA、P75的表达及与临床腰腿痛关系。方法该研究包括62例单节段腰椎间盘突出症手术患者,手术切除椎间盘组织应用免疫组织化学法检测NGF及其受体TrkA、P75的表达及应用ELISA法检测NGF蛋白表达水平。比较轻度退变及高度退变椎间盘NGF蛋白水平,应用多元线性回归分析椎间盘NGF蛋白水平的影响因素,患者腰腿痛及功能障碍分别采用VAS疼痛评分及ODI评分,比较不同的NGF蛋白水平对患者临床症状的影响。结果 NGF及其受体TrkA、P75均在椎间盘类软骨细胞中表达,NGF蛋白表达水平在轻度及高度退变椎间盘中无明显差异,NGF蛋白表达水平同NGF及其受体TrkA细胞阳性率明显相关,术前患者腰腿痛同NGF蛋白水平无明显相关,术后残留腰腿痛在高NGF水平组患者中更明显。结论腰椎间盘突出症患者中,椎间盘中存在NGF及其受体TrkA、P75的表达,椎间盘细胞自分泌NGF是椎间盘中NGF重要来源,术前椎间盘NGF水平同术后腰腿痛残留明显相关,这种结果显示椎间盘NGF促进腰腿痛的发生。

Objective To investigate the expression of nerve growth factor （NGF） and its receptor, tyrosine kinase A （TrkA） and p75 neurotrophin receptor （p75NTR） in discs from patients with lumbar disc herniation （LDH） and the effect of NGF on clinical symptoms. Methods Patients （n=62） with a single-level lumbar disc herniation treated by surgery were included, disc samples were obtained from patients during surgery. The expression of NGF, TrkA and P75NTR was detected by immunohistochemistry method. Protein levels were quantified using an enzyme-linked imnmnosorbent assay （ELISA） for NGF. Levels of NGF in the discs were compared between low-grade and high-grade degenerated discs. Multiple linear regression analysis was used to assess the factors affected to NGF level. Patient＇s symptoms were assessed using a visual analog scale （VAS） and the Oswestry disability index （ODI） ; the influence of NGF levels on pre- and post-operative symptoms was examined. Results hnmunopositive staining for NGF, TrkA and P75NTR was identified in the chondrocyte-like cells of the disc tissue. No significant differences in levels of NGF were found between low-grade and high-grade degenerated discs. The results of multiple linear regress analysis showed the cellular immunopositivity of NGF and TrkA are significantly related to NGF levels. Pre-operative symptoms were not related to NGF levels. Post-operative lower extremity pain and low back pain （LBP） were greater in patients with high levels of NGF. Conclusion This study demonstrates that NGF and its receptor, TrkA and P75 were expressed by disc cells and NGF is actually being produced by the chondrocyte-like cells of the disc tissue. Our results showed that pre-op-erative disc protein levels of NGF affected postoperative LBP and lower extremity pain, suggesting there is some degree of impact of NGF on generation of LBP and lower extremity pain.