三氧化二砷对类风湿关节炎滑膜细胞凋亡的影响——附18例报告  

The effects of As_2O_3 on the apoptosis of synoviocytes of rheumatoid arthritis——a report of 18 cases

作　　者：韩锋[1] 齐文成[1] 任洁[1] 张鸽[1] 

机构地区：[1]天津市第一中心医院风湿免疫科,300192

出　　处：《新医学》2009年第2期80-82,113,共4页Journal of New Medicine

基　　金：天津市卫生局科技基金资助项目(03KZ02)

摘　　要：目的:探讨三氧化二砷(As2O3)对类风湿关节炎(rheumatoid arthritis,RA)滑膜细胞凋亡的影响。方法:对18份RA滑膜组织进行原代培养,采用四甲基偶氮唑盐法检测加入0μmol/L、0.10μmol/L、0.40μmol/L、0.80μmol/L As2O3对RA滑膜细胞活力影响,用流式细胞仪分析加入不同浓度As2O3后早期凋亡细胞、晚期凋亡细胞、活细胞、坏死细胞所占的比例,观察加入不同浓度As2O3后RA滑膜细胞的半胱氨酸蛋白酶-3的活性变化。结果:与同一时段无加入As2O3的RA滑膜细胞比较,加入0.10μmol/L、0.40μmol/L、0.80μmol/L As2O3的RA滑膜细胞活力明显下降(均为P<0.05)。RA滑膜细胞中的早期凋亡细胞及坏死细胞所占比例随As2O3浓度升高而增高,活细胞所占比例随As2O3浓度升高而降低(均为P<0.05),其中,As2O3浓度为0.80μmol/L组的早期凋亡细胞及坏死细胞所占比例最高、活细胞所占比例最低(均为P<0.01)。半胱氨酸蛋白酶-3活性随As2O3浓度增加而增加(均为P<0.05)。结论:As2O3可抑制RA滑膜细胞的活力,在达到一定的药物浓度后可对滑膜细胞产生致死效应。As2O3所诱导滑膜细胞凋亡可能与半胱氨酸蛋白酶-3的活性增高有关。Objective： To investigate the effects of As2 O3 on apoptosis of synoviocytes of rheumatoid arthritis （RA）. Methods： Primary synoviocytes of 18 patients suffered from RA were cultured. The activity of synoviocytes incubated with different concentrations As2O3（0 μmol/L, 0. 10 μmol/L, 0. 40 μmol/L and 0. 80 μmol/ L） was detected by methyl thiazolyl tetrazolium （MTT）assay. The percentages of early and late apoptotic synoviocytes, percentages of live and dead synoviocytes were determined by flow cytometry. The production of caspase-3 by synoviocytes was examined. Results： The activity of synoviocytes incubated with different concentrations of As2O3 （0. 10 μmol/L, 0. 40 μmol/L and 0. 80 μmol/L）significantly decreased compared to synoviocytes without As2 O3 stimulation （P 〈 0. 05 ）. The percentages of early apoptotic and dead synoviocytes increased and the percentages of live synoviocytes decreased with increasing As2 O3 concentration （P 〈 0. 05 ）, with the highest percentage of early apoptotic and dead synoviocytes and the lowest percentage of live synoviocytes at 0. 80 μmol/L of As2O3 （P 〈 0. 01）. The activity of caspase-3 increased with increasing concentration of As2O3 （P 〈 0. 05 ）. Conclusion： As2O3 can inhibit the activity of RA synoviocyte, and can cause the death of RA synoviocyte at certain drug concentration. The apoptosis induced by As2O3 may be associated with increased capase-3 activity.

关 键 词：三氧化二砷 类风湿关节炎 滑膜细胞 细胞凋亡 半胱氨酸蛋白酶-3 

分 类 号：R593.22[医药卫生—内科学]