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  • 杨志高,张帆,陈智,程勇军,李凤宁,吕开阳,沈洪兴*,沈洪兴.退变颈椎椎间盘髓核中磷酸化p38 MAPK的表达[J].第二军医大学学报,2010,31(7):739-743    [点击复制]
  • YANG Zhi-gao, ZHANG Fan, CHEN Zhi, CHENG Yong-jun, LI Feng-ning, L Kai-yang, SHEN Hong-xing*,shenhongxing.Expression of phosphorylated p38 MAPK in nucleus pulposus of degenerated cervical intervertebral disc[J].第二军医大学学报,2010,31(7):739-743   [点击复制]
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退变颈椎椎间盘髓核中磷酸化p38 MAPK的表达
杨志高,张帆,陈智,程勇军,李凤宁,吕开阳,沈洪兴*,沈洪兴
0
(第二军医大学长海医院骨科,上海 200433)
摘要:
目的观察不同退变程度颈椎病患者椎间盘髓核(nucleus pulposus,NP)的病理改变及磷酸化p38 MAPK(phosphorylated p38 mitogen activated protein kinase,p-p38 MAPK)的表达差异,探讨颈椎椎间盘退变可能的分子机制。方法收集2008年10月至2009年5月在我院行手术治疗的35例颈椎病患者的NP组织,获取术前相应颈椎MRI(T2像正中矢状位)资料。其中男性25例,女性10例,年龄27~82岁, 5例来自单间隙,18例来自两间隙,12例来自三间隙;4例为C3/4、12例为C4/5、14例为C5/6、5例为C6/7。19例NP组织用于普通病理和免疫组织化学染色,16例用于蛋白质印迹分析。采用颈椎椎间盘MRI退变分级系统评定术前NP组织标本相应MRI退变程度。观察不同退变程度时NP组织的病理改变及p-p38 MAPK在NP组织中的定位;分析退变椎间盘中p-p38 MAPK含量与其MRI退变程度间的关系。结果随着颈椎椎间盘退变程度加重,NP内胶原纤维逐渐增多、增粗、变性,甚至聚合成团,NP逐渐纤维化;p-p38 MAPK定位于NP细胞胞核;NP细胞p-p38 MAPK表达阳性率随颈椎椎间盘退变程度加重逐渐升高,不同退变等级阳性表达的程度(阴性、弱阳性、强阳性),组间差异均有统计学意义(P<0.05);退变颈椎椎间盘中p-p38 MAPK的表达量(因变量Y)与椎间盘退变程度(自变量X)间存在线性关系:Y=0.423X-0.675 (P<0.05)。结论随退变程度加重,退变NP组织中正常组织逐渐被纤维组织替代,趋于纤维化;p-p38 MAPK定位于NP细胞胞核;其表达强度随退变加重而增强;p38 MAPK信号通路的激活可能是人颈椎椎间盘退变的机制之一。
关键词:  颈椎病  髓核  p38丝裂原活化蛋白激酶类  椎间盘退变
DOI:10.3724/SP.J.1008.2010.0739
投稿时间:2010-02-04最后修改时间:2010-05-17
基金项目:军队“十一五”医药卫生科研基金(06MA163).
Expression of phosphorylated p38 MAPK in nucleus pulposus of degenerated cervical intervertebral disc
YANG Zhi-gao, ZHANG Fan, CHEN Zhi, CHENG Yong-jun, LI Feng-ning, L Kai-yang, SHEN Hong-xing*,shenhongxing
(Department of Orthopaedics, Changhai Hospital, Second Military Medical University, Shanghai 200433, China)
Abstract:
ObjectiveTo observe the pathological changes of nucleus pulposus(NP)in cervical spondylosis patients and the expression of phosphorylated p38 mitogen activated protein kinase(p-p38 MAPK) in NP with the progression of cervical disc degeneration, in an attempt to explore the mechanism behind cervical disc degeneration.MethodsNP specimens were collected from 35 patients with cervical spondylosis, who received surgical treatment during October 2008 to May 2009 in our hospital.The preoperative MRI (T2-weighted midsagittal images) information of all patients was obtained.The 35 cases included 25 males and 10 females, with an age range of 27-82 years.Five specimens were from a single space, 18 from two spaces, and 12 from three spaces; 4 specimens were from C3/4, 12 from C4/5,14 from C5/6, and 5 from C6/7.Nineteen specimens were used for pathology and immunohistochemistry study and 16 for Western blotting analysis.The degrees of disc degeneration were assessed by MRI grading system for cervical intervertebral disc degeneration.The pathological changes of NP of different degeneration grades and the location of p-p38 MAPK in NP were observed, and the relationship between the p-p38 MAPK and the degrees of MRI degeneration was analyzed.ResultsWith the aggravation of discs degeneration, the collagen fibers within NP were increased, thickened, and degraded, forming clusters, and the NP gradually became fibrotic.Phosphorylated p38 MAPK located in the cell nucleus of NP tissues.The positive rate of p-p38 MAPK increased gradually with the aggravation of degeneration, and the expression degrees of p-p38 MAPK (negative, weakly positive, strongly positive) were significantly different between groups of different degeneration degrees(P<0.05).A linear relationship was found between p-p38 MAPK expression and the degeneration degrees of cervical disc:Y=0.423X-0.675 (P<0.05).ConclusionNormal tissues are gradually replaced by fibrotic tissues in degenerated NP.Phosphorylated p38 MAPK is located in the cell nucleus of NP cells; the p-p38 MAPK plays important roles in the cervical intervertebral discs degeneration.Expression of phosphorylated p38 MAPK in NP increases with the aggravation of degeneration, suggesting that activation of p38 MAPK signaling pathway may be one of the mechanisms for cervical disc degeneration.
Key words:  cervical spondylosis  nucleus pulposus  p38 mitogen-activated protein kinases  intervertebral disc degeneration