目的 探讨类风湿关节炎(RA)患者滑膜组织中磷酸化蛋白激酶(p-AKT)、B淋巴细胞瘤-2(Bcl-2)、基质金属蛋白酶-9(MMP-9)的表达水平,以及上述指标在RA发生发展中的意义。方法 选取2013-03至2022-03东部战区总医院骨科住院的RA患者15例和同期行膝关节手术的关节损伤患者10例,分别为RA组和对照组。收集两组患者滑膜组织病理标本及临床资料,对滑膜组织进行病理学观察并进行评分;采用免疫组织化学染色技术检测p-AKT、Bcl-2、MMP-9蛋白在滑膜组织中的表达情况,并与RA疾病活动指标之间进行相关性分析。结果 RA组与对照组在年龄、性别方面差异无统计学意义(P＞0.05)。RA组患者WBC、单核细胞计数(MONO)、中性粒细胞计数(NEUT)、C-反应蛋白(CPR)、类风湿因子(RF)、抗环瓜氨酸肽抗体(Anti-CCP)明显高于对照组(P＜0.05或P＜0.01);RA组患者滑膜组织Krenn’s病理评分明显高于对照组(P＜0.05或P＜0.01)。与对照组比较,RA组滑膜组织中p-AKT、Bcl-2、MMP-9的表达明显高于对照组(P＜0.05或P＜0.01)。在RA组滑膜组织中,p-AKT的表达与红细胞沉降率(ESR)(r=0.680,P=0.005)、DAS28-3(r=0.634,P=0.011)呈正相关;Bcl-2的表达与ESR(r=0.640,P=0.010)、CRP(r=0.584,P=0.022)呈正相关;MMP-9的表达与ESR(r=0.809,P=0.000)、RA疾病活动评分(DAS28-3)(r=0.590,P=0.021)呈正相关。Bcl-2与MMP-9的表达呈正相关(r=0.630,P=0.012)。结论 RA患者滑膜组织中p-AKT、Bcl-2、MMP-9的表达增加,与RA疾病活动相关指标呈正相关。RA患者滑膜过度增殖,可能与AKT相关信号途径的激活、凋亡抑制蛋白Bcl-2过表达有关。
Abstract
Objective To explore the expression and clinical significance of phosphorylated protein kinase B (p-AKT), B-lymphoma-2 (Bcl-2) and matrix metalloproteinase-9 (MMP-9) in synovial tissues of patients with rheumatoid arthritis (RA). Methods Fifteen patients with RA who were hospitalized in orthopedics department of General Hospital of Eastern Theater Command from March 2013 to March 2022 were included in the RA group, while 10 patients with joint injuries who underwent knee surgeries during the same period were included in the control group. Synovial histopathological specimens and clinical data of RA patients were collected. Synovial tissue characteristics were assessed from a pathological perspective. Immunohistochemical staining was used to detect the expression of p-AKT, Bcl-2 and MMP-9 proteins in the synovial tissues of RA patients. Results There was no significant difference in age or gender between two groups (P>0.05). White blood cells (WBC), monocytes (MONO), neutrophils (NEUT), c-reactive protein (CPR), rheumatoid factors (RF) and anti-cyclic citrullinated peptide antibody (Anti-CCP) in RA group were significantly higher than those in the control group (P<0.05 or P<0.01). The Krenn’s pathological score of synovial tissues in the RA group was significantly higher than that in the control group (P<0.05 or P<0.01). Compared with the control group, the expressions of p-AKT, Bcl-2 and MMP-9 in the synovial tissue of the RA group were significantly higher than those of the control group (P<0.05 or P<0.01). The expression of p-AKT was positively correlated with ESR (r=0.680, P=0.005) and DAS28-3 (r=0.634, P=0.011). The expression of Bcl-2 was positively correlated with erythrocyte sedimentation rate (ESR) (r=0.640, P=0.010) and CRP (r=0.584, P=0.022). The expression of MMP-9 was positively correlated with ESR (r=0.809, P=0.000) and Disease Activity Score 28-3 (DAS28-3) (r=0.590, P=0.021). The expression of Bcl-2 and MMP-9 was positively correlated (r=0.630, P=0.012). Conclusions The expressions of p-AKT, Bcl-2 and MMP-9 increase in the synovial tissues of RA patients, which is positively correlated with indicators related with RA disease activity. The Overproliferation of synovium in RA patients may be related with the activation of AKT-related signaling pathways and the overexpression of apoptosis inhibitory protein Bcl-2.
关键词
类风湿关节炎 /
滑膜组织 /
滑膜病理 /
免疫组织化学 /
p-AKT /
Bcl-2 /
MMP-9
Key words
rheumatoid arthritis /
synovial tissue /
synovial pathology /
immunohistochemistry /
p-AKT /
Bcl-2 /
MMP-9
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基金
2007年军队系统国家中医药管理局重点专科(专病)建设项目(2007ZDZB001)
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