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    血清软骨代谢标志物及自噬基因在膝骨关节炎和类风湿性关节炎中的变化研究

    Changes of serum cartilage metabolic markers and autophagy genes in patients with knee osteoarthritis and rheumatoid arthritis

    • 摘要: 目的 检测血清软骨标志物Ⅰ型胶原交联C末端肽(CTX-Ⅰ)、Ⅱ型胶原羧基端端肽(CTX-Ⅱ)、金属蛋白酶13(MMP-13)和自噬相关基因Beclin-1、LC3-Ⅱ在膝关节骨关炎患者(KOA)和类风湿性关节炎患者(RA)中的变化,探讨其对KOA和RA的筛查和诊断意义。方法 收集2022年2月-2023年3月就诊于徐州市第一人民医院和徐州市中心医院的KOA(n=57)和RA(n=58)患者,另选择60岁以上老年健康体检志愿者(EC,n=50)和35岁以下年轻健康体检志愿者(YC,n=60)。采用酶联免疫吸附法(ELISA)检测所有受试者血清软骨标志物CTX-1、CTX-2和MMP-13,分析其外周血Beclin-1和LC3-Ⅱ的RNA表达量,比较各组之间差异,并绘制受试者工作曲线(ROC)确定最佳临界值。结果 KOA组和RA组血清CTX-Ⅰ、CTX-Ⅱ和MMP-13水平均高于EC组,RA组血清CTX-Ⅱ水平高于KOA组(P<0.05),而血清CTX-Ⅰ和MMP-13水平2组间差异无统计学意义,YC组中自噬基因Beclin-1和LC3-Ⅱ的RNA表达量明显高于其他组 (P<0.05或<0.01)。ROC曲线分析显示:血清CTX-Ⅰ、CTX-Ⅱ和MMP-13水平对RA和KOA具有诊断价值,ROC曲线下面积(AUC)分别为0.789、0.858、0.619和0.769、0.675、0.748,多指标联合诊断的AUC分别为0.876和0.814。结论 血清中较高的CTX-Ⅰ、CTX-Ⅱ和MMP-13水平和低表达的自噬基因可能是导致KOA和RA患者骨破坏活动增强的重要因素,并能起到良好的诊断作用。

       

      Abstract: Objective To detect the changes of serum cartilage markers type Ⅰ collagen cross-linked C-terminal peptide (CTX-Ⅰ), type Ⅱ collagen carboxy-terminal peptide (CTX-Ⅱ), metalloproteinase 13 (MMP-13) and autophagy related genes Beclin-1 and LC3-Ⅱ in patients with osteoarthritis (KOA) and rheumatoid arthritis (RA), in order to explore its significance in the screening and diagnosis of KOA and RA.Methods Patients with KOA and RA who were admitted to Xuzhou First People's Hospital and Xuzhou Central Hospital from February 2022 to March 2023 were selected,including 57 KOA patients and 58 RA patients. Meanwhile, 50 healthy subjects over 60 years old and 60 healthy subjects under 35 years old who underwent health examination were also selected. The levels of serum cartilage markers CTX-1, CTX-2 and MMP-13 were detected by ELISA. The RNA levels of Beclin-1 and LC3-Ⅱ in peripheral blood among all groups were compared, and the diagnostic threshold was determined by plotting a receiver operating curve (ROC).Results The levels of serum CTX-Ⅰ, CTX-Ⅱ and MMP-13 in the KOA and RA groups were higher than those in the control group. The levels of serum CTX-Ⅱ in the RA group were higher than those in the KOA group (P<0.05), but there was no statistical difference in serum CTX-Ⅰ and MMP-13 levels between the two groups. The RNA levels of Beclin-1 and LC3-Ⅱ in the YC group were significantly higher than those in other groups (P<0.05 or <0.01). ROC curve analysis showed that serum CTX-Ⅰ, CTX-Ⅱ and MMP-13 showed diagnostic values for RA and KOA, and the area under ROC curve (AUC) were 0.789, 0.858, 0.619 and 0.769, 0.675, 0.748, respectively, and the AUC of combined diagnosis of multiple indicators were 0.876 and 0.814, respectively.Conclusions High levels of CTX-Ⅰ, CTX-Ⅱ and MMP-13 in serum and low levels of autophagy genes may be important factors leading to enhanced destructive activity in patients with KOA and RA, and can play a good role in diagnosis.

       

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