骨关节炎软骨破坏与凋亡相关蛋白survivin、caspase-3和bcl-xl的表达的相关性研究

目的 研究骨关节炎(OA)患者关节软骨细胞凋亡和软骨破坏的关系,为用药物控制凋亡作为治疗OA的潜在治疗策略提供理论依据.方法 应用原位凋亡方法(TUNEL)检测OA患者(n=20)以及以股骨颈骨折患者为对照组(n=8)的关节软骨细胞的凋亡情况,并通过凋亡软骨细胞的分布来半定量地评估软骨的破坏程度;应用免疫组织化学方法检测凋亡相关蛋白survivin(SVV)、caspase-3和bcl-xl的表达,研究OA软骨破坏与凋亡蛋白表达的相关性.结果 在软骨破坏的相对早期即可以检测凋亡软骨细胞,而且与软骨破坏的程度显著相关(r=0.476,P=0.007),正常对照组组织则含有较少凋亡细胞(P=0.000).SVV表达在有降解损害的软骨细胞和软骨表层细胞中,与正常对照组之间差异有统计学意义(r=0.413,P=0.008),而且与TUNEL染色阳性凋亡细胞的数量有一定的相关性.与SVV相比,caspase-3表达范围较广,在相对正常的软骨区域也可检测到.软骨组织中未见明确的bcl-xl蛋白表达.结论 OA软骨细胞凋亡的程度与软骨破坏程度密切相关,在软骨的降解损害过程中,SVV和caspase-3蛋白的表达对OA软骨细胞的凋亡过程起到一定的作用.

Correlation of apoptosis of articular chondrocytes in osteoarthritis with degree of cartilage destruction and expression of apoptosis-related proteins: surviving, caspase-3, anti Bcl-xl

Objective To investigate the relationship of chondroeyte apoptosis to cartilage destruction in osteoarthritis (OA). Methods Specimens of cartilage were collected from 20 OA patients and 8 patients with femoral neck fracture during operation. TUNEL method was performed to semi-quantitatively detect the distribution of apoptotic chondrocytes. Immunohistochemistry was used to detect the expression of the apoptosis-associated proteins : surviving ( SVV ), caspase-3, and apoptosis regulating protein Bc]-2.Results Apoptotic chondrocytes were identified in a relatively early phase of cartilage destruction, and correlated positively and significantly with the degree of cartilage degeneration. In contrast, the specimens of normal subjects contained few cells with apoptotic changes ( P = 0. 000 ＜ 0. 05 ). The TUNRL positive cell rate of the OA group was significantly higher than that of the control group ( P = 0. 000). Protein expression of SVV was observed in the chondrocytes within the degraded lesions and in the chondrocytes of the superficial layers, and showed a kind of positive correlation with the number of TUNEL-stained cells. The distribution area of easpase-3 was greater than that of SVV, and could be detected in relatively normal cartilage areas. Protein expression of Bcl-xl was not definitely detected in cartilage tissue. Conclusion The degree of chondrocyte apoptosis is closely related to cartilage destruction. The protein expression of SVV and easpase-3 may reflect the involvement of these proteins in the apoptotic process in the articular chondrocytes in OA.