四种血清生物标志物联合检测早期诊断和评价骨关节炎的价值

Early diagnosis value of combination detection of four serum biomarkers for osteoarthritis

背景:文献报道显示生物标志物在诊断早期骨关节炎方面有其独特优势,但到目前为止,人们对这些生物标志物诊断人类早期骨关节炎方面的应用价值尚不清楚。目的:定量检测新西兰大白兔血清中Ⅱ型胶原C-端肽、基质金属蛋白酶3、肿瘤坏死因子α、白细胞介素1水平的变化,探讨其作为骨关节炎早期诊断及病情评估指标的价值和意义。方法:新西兰大白兔35只,实验组(28只)切除韧带和半月板进行造模,分别在造模1,2,3,4周后分批进行血清生物标志物Ⅱ型胶原C-端肽、基质金属蛋白酶3、肿瘤坏死因子α、白细胞介素1水平的检测,以及膝关节MRI检查,关节样本大体观察,组织病理学观察。对照组(7只)不做韧带和半月板的切除,同样在上述4个时间点检测4种生物标志物水平;术后4周行膝关节MRI检查、关节样本大体观察、组织病理学观察。结果与结论:实验组术后各时间点4种生物标志物水平均高于对照组,差异有显著性意义(P<0.05);术后1周,组织病理学变化及膝关节MRI信号改变不明显;术后2周,出现骨关节炎特征性病理变化和膝关节MRI信号改变;术后3,4周,骨关节炎特征性病理变化和膝关节MRI信号改变更加明显;而4种生物标志物在膝关节未出现明显病理学变化和明显MRI改变时即已增高。结果可见血清Ⅱ型胶原C-端肽、基质金属蛋白酶3、肿瘤坏死因子α、白细胞介素1的联合检测,可作为骨关节炎早期诊断和病情评估的参考指标。

BACKGROUND： Studies have shown that biomarkers in the diagnosis of early osteoarthritis have their unique advantages, but so far, it is not clear on application value of biomarkers in the diagnosis of earlyosteoarthritis in human being. OBJECTIVE： To investigate the value and significance as early diagnosis and condition assessment indicators of osteoarthritis by means of quantitative detection of the changes in C-telopeptide of collagen type Ⅱ, matrix metalloproteinase protein-3, tumor necrosis factor-α, and interleukin-l. METHODS： Thirty-five New Zealand white rabbits were divided into experimental group （n=28） and control group （n=7）. Resection of the ligament and meniscus was performed in the experimental group for modeling. No treatment was done in the control group. C-telopeptide of collagen type Ⅱ, matrix metalloproteinase protein-3, tumor necrosis factor-α, and interleukin-1 levels were detected at 1,2, 3, 4 weeks after modeling in the experimental group, and these biomarkers were also detected in the control group at the same time points. Knee MRI examination, joint sample general observation and histopathological observation were conducted. RESULTS AND CONCLUSION： Levels of four biomarkers in the experimental group were significantly higher than those in the control group at each time point after modeling （P 〈 0.05）. Histopatological changes and knee MRI variation did not occur at 1 week after operation; however, these changes appeared at 2 weeks, and strengthened at 3-4 weeks. In addition, the levels of four biomarkers began to increase at 1 week after operation The results suggest that combination detection of C-telopeptide of collagen type Ⅱ, matrix metalloproteinase protein-3, tumor necrosis factor-α, and interleukin-1 in serum can become a reference indicator for early diagnosis and assessment of osteoarthritis.