雷公藤甲素抑制类风湿关节炎患者外周血单个核细胞分泌TNF-α及其基因多态性的关系  

Correlation between the Inhibitory Effect of Triptolide on the Secretion of Tumor Necrosis Factor-α(TNF-α) by the Peripheral Blood Mononuclear Cells(PBMC) and the Gene Polymorphisms of TNF-α in Patients with Rheumatoid Arthritis

作　　者：熊日波[1] 涂胜豪[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院中西医结合研究所,武汉430030

出　　处：《医药导报》2007年第10期1124-1127,共4页Herald of Medicine

基　　金：国家自然科学基金资助项目(基金编号:90209049)

摘　　要：目的探讨雷公藤甲素(TP)抑制类风湿性关节炎(RA)患者外周血单个核细胞(PBMC)分泌肿瘤坏死因子α(TNF-α)及其基因多态性的关系。方法采用特异基因等位引物PCR法,对RA患者TNF-α基因启动子区-308位点G-A多态性进行基因型检测,同时进行PBMC培养,用脂多糖(LPS)刺激培养细胞,并予以1.0,5.4和15.0 ng.mL-1雷公藤甲素处理PBMC,收集培养上清液,酶联免疫吸附试验(ELISA)检测上清液中TNF-α的含量。结果低剂量TP处理后,与单纯用LPS处理比较,AA,AG基因型组TNF-α分泌量的下降幅度分别为3.80%,4.91%和20.74%(P>0.05),而GG基因型组TNF-α的下降幅度达20.74%(P<0.05)。中剂量TP处理后,与单纯用LPS处理比较,AA,AG和GG基因型组TNF-α的下降幅度分别为20.42%,34.73%和41.69%(P<0.05)。但用高剂量TP处理后,TNF-α的分泌量略有升高,但在这三种基因型组中差异无显著性(P>0.05)。结论RA患者TNF-α基因-308位点多态性与TNF-α的分泌量相关,不同浓度的TP对不同基因型的TNF-α抑制作用有差异,这可能是导致TP药理作用出现个体差异的原因之一。Objective To explore whether the inhibitory effect of triptolide （TP）on the secretion of TNF-a by the PBMC is correlated with the TNF-α gene polymorphisms in patients with rheumatoid arthritis（ RA ）. Methods The gene polymorphism of the G-A site 308 in the promotor region of the TNF- α gene in 42 patients with RA was assayed with the AS- PCR. In the meantime, PBMC from the patients were cultured and stimulated with LPS, followed by treatment of the cells with TP in concentrations of 1.0,5.4 and 15.0 mg· mL^-1 , respectively. Contents of TNF- α in the supernatants were determined with ELISA. Results When treated with low dose TP, the rates of decrease in the TNF-α secretion by the AA and AG genotypes were 3.80% and 4.91% , respectively, the differences being insignificant as compared with those of the control groups treated only with LPS（P 〉0.05）. In the same experiment, however, the decrease rate in the TNF- α secretion by the GG genotype was 20.74% （P 〈0.05）. When treated with medium dose of TP, the rates of decrease in the TNF- α secretion by the AA , AG and GG were 20.42% ,34.73% and 41.69%, respectively, the differences being all statistically significant as compared with those of the control groups treated only with LPS（ P 〈 0.05 ）. When treated with high dose TP, the TNF- α secretion by the 3 genotypes showed no significant differences as compared with those of the control groups treated only with LPS（ P 〉 0.05 ）. Conclusion Gene polymorphism at the TNF-α-308 sites was shown to be correlated with the secretion of TNF-α in the patients with RA. TP in different concentrations showed different inhibitory effects on the TNF- α secretion in patients carrying different genotypes, which may be one of the reasons for the phenomenon that people respond differently to TP.

关 键 词：雷公藤甲素 关节炎 类风湿 单核细胞 肿瘤坏死因子 基因多态性 

分 类 号：R967[医药卫生—药理学]