氨基葡萄糖胶囊干预膝骨关节炎患者外周血单个核细胞中软骨代谢相关基因的表达

Effect of glucosamine capsule on cartilage metabolism-related genes in peripheral blood mononuclear cells of patients with knee osteoarthritis

背景:目前关于氨基葡萄糖的研究多集中于对膝骨关节炎的治疗作用,但关于其对膝骨关节炎患者外周血中软骨代谢相关基因影响的研究有限。目的:观察氨基葡萄糖胶囊对膝骨关节炎的治疗效果及对软骨代谢相关基因表达的影响。方法:选取2017年3月至2019年2月郑州大学附属郑州中心医院收治的90例膝骨关节炎患者,另选取同期医院体检中心收入的40例健康受试者,检测并对比健康受试者与膝骨关节炎患者治疗前外周血单个核细胞中软骨寡聚基质蛋白、Ⅱ型胶原纤维α1、聚糖蛋白、特异性组织抑制物3基因表达水平。采用随机数表法将膝骨关节炎患者分为常规组和研究组,分别给予双氯芬酸钠缓释片、双氯芬酸钠缓释片+氨基葡萄糖胶囊治疗12周,对比治疗前后2组外周血单个核细胞中各基因表达水平、Lequesne指数,统计治疗期间2组不良反应发生情况。结果与结论:①与健康受试者比较,膝骨关节炎患者外周血单个核细胞中软骨寡聚基质蛋白、特异性组织抑制物3 mRNA相对表达量升高(P<0.05),Ⅱ型胶原纤维α1、聚糖蛋白mRNA相对表达量降低(P<0.05);②治疗前研究组和常规组外周血单个核细胞中各基因表达水平比较,差异均无显著性意义(P>0.05);治疗后2组外周血单个核细胞中软骨寡聚基质蛋白、特异性组织抑制物3 mRNA相对表达量均低于治疗前,且研究组低于常规组(P<0.05);治疗后2组外周血单个核细胞中Ⅱ型胶原纤维α1、聚糖蛋白mRNA相对表达量均高于治疗前,且研究组高于常规组(P<0.05);③治疗前研究组和常规组Lequesne指数比较,差异均无显著性意义(P>0.05);治疗后2组Lequesne指数均低于治疗前,且研究组低于常规组(P<0.05);④研究组和常规组不良反应发生率比较,差异均无显著性意义(P>0.05);⑤结果表明,氨基葡萄糖胶囊可有效改善膝骨关节炎患者临床症状且安全可靠,可能通过抑制软骨寡聚基质蛋白、特异性组织抑制物3基因表达,促进Ⅱ型胶原纤维α1、聚糖蛋白基因表达实现的。

BACKGROUND:At present,the research on glucosamine mostly focused on the treatment of knee osteoarthritis,but the research on the effect of glucosamine on cartilage metabolism-related genes in peripheral blood of patients with knee osteoarthritis is limited.OBJECTIVE:To observe the effect of glucosamine capsule on knee osteoarthritis and the expressions of cartilage metabolism-related genes.METHODS:Totally 90 knee osteoarthritis patients admitted to the Zhengzhou Central Hospital Affiliated to Zhengzhou University from March 2017 to February 2019 were selected,and 40 healthy subjects from the medical examination center in the same period were selected as healthy subjects.The cartilage oligomeric matrix protein(COMP),type II collagen fiberα1 gene(COL2A1),glycoprotein and specific tissue inhibitor(TIMP)-3 gene expression levels in peripheral blood mononuclear cells were detected and compared between healthy subjects and knee osteoarthritis patients before treatment.Knee osteoarthritis patients were divided into routine group and study group by random number table,and they were treated with diclofenac sodium sustained-release tablets,diclofenac sodium sustained-release tablets and glucosamine capsules,respectively.Both groups were treated for 12 weeks.The levels of gene expressions and Lequesne index in peripheral blood mononuclear cells of two groups were compared before and after treatment.During the treatment,the occurrence of adverse reactions was counted in the two groups.RESULTS AND CONCLUSION:(1)The relative expressions of COMP and TIMP-3 in peripheral blood mononuclear cells of knee osteoarthritis patients were higher than those of healthy subjects(P<0.05),while the mRNA relative expressions of COL2A1 and glycoprotein were lower than those of healthy subjects(P<0.05).(2)There were no significant difference in gene expression levels in peripheral blood mononuclear cells before treatment between study group and routine group(P>0.05).The mRNA relative expressions of COMP and TIMP-3 in peripheral blood mononuclear cells of the two groups after treatment were lower than those before treatment,and those of the study group were lower than those of the routine group(P<0.05).The mRNA relative expressions of COL2A1 and glycoprotein in peripheral blood mononuclear cells of the two groups after treatment were higher than those before treatment,and the mRNA relative expressions of COL2A1 and ACAN in the study group were higher than those in the routine group(P<0.05).(3)There was no significant difference in Lequesne index between the study group and the routine group before treatment(P>0.05).Lequesne index in both groups after treatment was lower than that before treatment,and that in the study group was lower than that in the routine group(P<0.05).(4)There was no significant difference in the incidence of adverse reactions between the study group and the routine group(P>0.05).(5)Results suggest that glucosamine capsule can effectively improve the clinical symptoms of patients with knee osteoarthritis.It is safe and reliable.It may promote the expression of COL2A1 and glycoprotein genes by inhibiting the expression of COMP and TIMP-3 genes.