摘要
目的研究不同浓度甲氨蝶呤（MTX）、硫酸羟氯喹（HCQ）、环磷酰胺（CTX）和来氟米特（LEF）活性代谢产物A771726对人单核细胞糖皮质激素受体α（GRα）mRNA表达的影响。方法对培养的人单核细胞株THP-1给予不同浓度的MTX、HCQ、CTX、A771726，以地塞米松（DEX）为阳性对照，36h后采用Real-time PCR法检测GRαmRNA的表达。采用Kruskal—Wallis日检验和Nemenyi法检验进行统计学处理。结果36h后DEX明显下调THP-1细胞上GRαmRNA的表达（P〈0．05）；不同浓度的A771726均下调GRαmRNA的表达（P〉0．05）；高、中浓度的MTX、HCQ、CTX亦下调THP-1细胞的GRαmRNA的表达（P〉0．05）；与空白组比较，低浓度的MTX、HCQ、CTX可以使THP-1细胞的GRαmRNA表达上调（P〉0．05）；与阳性对照组比较，低浓度的MTX、HCQ、CTX亦可以使THP-1细胞的GRαmRNA表达上调（P〈0．05）。结论低浓度的MTX、HCQ、CTX上调GRαmRNA表达可能是其治疗自身免疫病的作用机制之一。
Objective To investigate the effects of methotrexate （MTX）, hydroxychloroquine （HCQ）, cyclophosphamideon （CTX） and active metabolite of Leflunomide （LEF）-A771726 on the expression of glucocorticoid receptorα （GRα） mRNA in human monocyte cell line human myeloid leukemia mononuclear ceils （THP）-1. Methods Cultured THP-1 cells were stimulated by MTX, HCQ, CTX, and A771726 with different concentrations, with dexamethasone （DEX） as positive control, after 36 h the GRα mRNA expressions were examined by real-time polymerase chain reaction （ PCR）. Data analysis was performed with Kruskal-Wallis H test and Nemenyi test. Results After 36 h, DEX decreased significantly the expression of GRα mRNA in THP-1 cells （ P 〈0. 05） ; A771726 with different concentrations had reduced expression of GRα mRNA （ P 〉 0.05 ） ; high and medium concentration of MTX, HCQ and CTX decreased the expression of GRα mRNA in THP-1 cells （ P 〉 0. 05）. Compared to the blank control, low concentration of MTX, HCQ, and CTX increased the expression of GRα mRNA in THP-1 ceils （ P 〉 0. 05） ; Compared to the positive control, low concentration of MTX, HCQ, and CTX increased the expression of GRα mRNA in THP-1 cells （ P 〈0. 05）. Conclusions Low dose MTX, HCQ, and CTX-increased GRα mRNA may be one of the mechanism of action of the treatment of autoimmune diseases.
出处
《中国医师杂志》
CAS
2016年第6期829-832,836,共5页
Journal of Chinese Physician
基金
黑龙江省教育厅科学技术研究项目（11551156）
