重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白联合芍药苷对人滑膜细胞增殖的影响及部分机制  

The influence of Paeoniflorin and recombinant human type Ⅱ tumor necrosis factor receptor-antibody fusion protein on human synovial cells and part mechanism

作　　者：解国雄[1] 吴华勋[1] 陈镜宇[1] 魏伟[1] 

机构地区：[1]安徽医科大学临床药理研究所,抗炎免疫药理学教育部重点实验室,抗炎免疫药物安徽省工程技术研究中心,安徽省中药研究与开发重点实验室,合肥230032

出　　处：《安徽医科大学学报》2012年第7期809-812,共4页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:30973543;81173075);安徽省高校自然科学基金(编号:KJ2011Z181;KJ2011Z180)

摘　　要：目的观察重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白(rhTNFR:Fc)与芍药苷(Pae)联合应用对人成纤维样滑膜细胞(FLS)增殖的影响,探讨其对肿瘤坏死因子受体(TNFR)信号通路的调节作用。方法经知情同意,收集行髋关节置换术患者正常滑膜组织,采用组织块培养法对人滑膜细胞进行培养。取第3代人FLS,用肿瘤坏死因子α(TNF-α,20μg/L)刺激,分别用rhTNFR:Fc(10 mg/L)、Pae(10-5mol/L)及二者联合干预。MTT法检测人FLS的增殖反应,免疫组化法半定量分析肿瘤坏死因子受体1(TNFR1)、肿瘤坏死因子受体相关因子2(TRAF2)、肿瘤坏死因子受体相关死亡结构蛋白(TRADD)在FLS中的表达情况。结果 rhTNFR:Fc与Pae联合用药对FLS增殖的抑制作用优于rhTNFR:Fc和Pae单独给药组。rhTNFR:Fc、Pae及联合用药均能明显下调FLS中TNFR1和TRAF2表达,上调TRADD表达;与单独用药相比,联合用药能进一步上调TRADD表达,而对TNFR1和TRAF2的表达无明显影响。结论 rhTNFR:Fc和Pae联合用药对人FLS增殖的抑制作用优于单独给药,其作用机制可能与调节TRADD有关。Objective To investigate the regulatory effects of rhTNFR： Fc and Paeoniflorin （Pae） combination therapy on fibroblast-like synovioeyte （FLS） proliferation, and to explore the regulatory role of Pae on the TNFR signaling pathway. Methods Informed consent, we collected normal synovial tissue of patients with hip arthroplasty, and cultured human synovial cells with tissue block method. Took the three generations of FLS, and then gave Pae（ 10-5 mol/L）and rhTNFR：Fe（ 10 mg/L）and combination therapy. The proliferative response of human FLS was detected by MTT method, and TNFR1, TRAF2, TRADD expression in FLS were detected by semi-quantitative analysis of the immunohistoehemieal method. Results The proliferation experiments showed that the Pae and rhTNFR ： Fc combination therapy group on the efficacy of F1S proliferation, which were better than that of the Pae alone group. Immunohistochemical experiments showed that Pae and rhTNFR： Fc both could downregulate the TNFR1 and TRAF2 expression, and upregulate TRADD expression in FLS. Conclusion Pae and rhTNFR： Fc combination therapy is superior to monotherapy with FLS, and the mechanism may be achieved by regulating the TRADD.

关 键 词：芍药苷 重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白 滑膜细胞 增殖 肿瘤坏死因子受体 

分 类 号：R967[医药卫生—药理学] R969.3[医药卫生—药学]