大骨节病死亡受体途径调节因子表达的组织学改变

Changes of death receptor regulator expression in the articular cartilage of patients with Kashin-Beck disease

目的观察大骨节病软骨组织中Fas相关死亡结构域蛋白(FADD)和细胞FLICE抑制蛋白(c-FLIP)表达的变化,明确其在大骨节病软骨损伤中的作用。方法将依据大骨节病和骨关节病诊断标准收集的软骨分为大骨节病组(KBD)、骨关节病组(OA)和正常对照组。采用免疫组化染色法检测3组关节软骨的死亡受体调节因子FADD和c-FLIP表达变化,并在显微镜下计数和比较3组关节软骨不同层间阳性表达率的显著性差异。结果(1)KBD和OA组软骨[分别为(28.68±2.19)%和(35.40±2.34)%]中层FADD表达显著较正常组增高(F=16.245,P=0.000),而在表、深层3组间均无显著差异(P=0.206,P=0.761);(2)FADD在KBD软骨中表达以中层最高,为(28.68±5.38)%,其次为深层的(17.94±8.38)%;(3)KBD和OA软骨表层FLIP表达均显著低于正常组(F=5.929,P=0.018),而中层和深层与正常组间均无显著差异。结论 KBD软骨中层FADD显著上调,而软骨表层FLIP表达显著下调,表明死亡受体途径及其调节因子在大骨节病软骨损伤中具有重要作用。

Objective To investigate the changes in the expressions of Fas-associated death domain protein（FADD） and cellular-FLICE inhibitory protein（c-FLIP） in the articular cartilage of patients with Kashin-Beck disease（KBD） and the role of these proteins in the pathogenesis of KBD.Methods The cartilage samples were collected from patients with established diagnosis of KBD and osteoarthritis and from healthy control subjects undergoing amputation due to traffic accidents.The expressions of Fas-associated death domain protein（FADD） and cellular-FLICE inhibitory protein（c-FLIP） in the cartilage were detected by immunohistochemistry,and the positive chondrocytes were counted in different layers of the articular cartilage under microscope.Results The positivity rates of FADD in the middle layer of articular cartilage from patients with KBD [（28.68±2.19）%] and osteoarthritis [（35.40±2.34）%] were significantly higher than that in normal cartilage [（10.51±5.02）%,F=16.245,P=0.000],but the rates in the upper and deeper layers were comparable among the 3 groups（P=0.206-0.761）.In KBD cartilage,FADD expression was the highest in the middle layer [（28.68±5.38）%] followed by the deeper layer [（17.94±8.38）%].Compared with the healthy controls,KBD and osteoarthritis patients showed significantly higher FLIP expression in the upper layer of the cartilage（F=5.929,P=0.018） but similar expressions in middle and deeper layers.Conclusions KBD patients have significant increased FADD expression in the middle layer but decreased FLIP expression in the upper layer of the cartilage,suggesting that the death receptor pathway and its regulators play important roles in the pathogenesis of KBD.