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背景:AG490是新近发现的一种JAK激酶抑制剂,可以和受体酪氨酸激酶竞争结合位点,从而通过阻断JAK/STAT通路达到抑制γ-干扰素等器官移植排斥反应相关细胞因子活化,进而抑制器官抑制排斥反应。目的:验证AG490作为免疫抑制剂的可能性及其基本作用途径,并与环孢素A及他克莫司相比较。设计、时间及地点:对照观察,于2007-10/2008-04在福建省协和医院泌尿外科研究所完成。材料:AG490购自美国SIGMA公司。方法:取8位健康成年人外周静脉血,密度梯度法分离淋巴细胞,分别应用植物血凝素、白细胞介素2、淋巴细胞混合培养诱导人淋巴细胞产生增殖。主要观察指标:分别采用酶联免疫吸附法检测在AG490、环孢素A、他克莫司作用下人淋巴细胞(T,B混合存在)增殖过程中细胞因子白细胞介素2、白细胞介素6、γ-干扰素的质量浓度。结果:在体外实验中,AG490对于植物血凝素、白细胞介素2刺激及淋巴细胞混合培养引起的人淋巴细胞增殖反应中白细胞介素2、γ-干扰素的分泌可以起到抑制作用(P<0.05),但对于白细胞介素6分泌无抑制作用(P<0.05),此作用与临床常用免疫抑制剂环孢素A、他克莫司相类似。结论:AG490有可能是一种潜在的免疫抑制剂。
BACKGROUND: AG490 is a recently discovered JAK kinase inhibitor that competes with receptor tyrosine kinases for binding sites and thus inhibits the activation of cytokines associated with rejection following organ transplant rejection by blocking the JAK / STAT pathway , Thereby inhibiting the organ rejection rejection. OBJECTIVE: To verify the possibility of AG490 as an immunosuppressant and its basic route of action, compared with cyclosporine A and tacrolimus. DESIGN, TIME AND SETTING: The comparison study was performed at the Urological Institute, Union Hospital, Fujian Province from October 2007 to April 2008. Material: AG490 from the United States SIGMA company. Methods: Peripheral venous blood was collected from 8 healthy adults and lymphocytes were separated by density gradient method. The proliferation of human lymphocytes was induced by mixed culture of phytohemagglutinin, interleukin - 2 and lymphocytes respectively. MAIN OUTCOME MEASURES: The levels of cytokines interleukin 2, interleukin 6 (IL-6) and interleukin-6 (IL-6) were measured by enzyme linked immunosorbent assay (ELISA) in the proliferation of human lymphocytes (mixed with T and B) under the action of AG490, cyclosporin A and tacrolimus , Γ-interferon mass concentration. Results: In vitro, the effect of AG490 on the secretion of interleukin 2 and interferon-γ in human lymphocyte proliferation induced by phytohemagglutinin, interleukin-2 stimulation and lymphocyte mixed culture (P <0.05), but no effect on the secretion of IL-6 (P <0.05). This effect is similar to that of cyclosporine A and tacrolimus, which are commonly used in clinical practice. Conclusion: AG490 may be a potential immunosuppressive agent.