含噻唑烷-4-酮类核苷的免疫调节功能研究

目的 利用小鼠脾细胞实验建立的免疫活性研究平台,进一步阐明含噻唑烷-4-酮环类核苷的免疫增强活性,并评价其作为药物的潜在开发价值.方法通过体外细胞学实验观察含噻唑烷-4-酮环糖类衍生物CH1a、CH2a、CH1b和CH2b对丝裂原刀豆蛋白A(Con A)、脂多糖(LPS)]处理的脾淋巴细胞增殖能力的影响,用酶联免疫吸附测定(ELISA) 法检测CH1a、CH2a、 CH1b、CH2b对淋巴细胞产生的细胞因子白细胞介素(IL) 2、IL-4和γ干扰素(IFN-γ)的影响.所有实验指标均与免疫调节药匹多莫德比较.结果化合物CH1a、CH2a、CH1b和CH2b均可增强ConA处理脾细胞的增殖能力,与匹多莫德比较差异有统计学意义(P＜0.01);CH1b和CH2b可促进LPS处理的脾细胞增殖,作用明显强于匹多莫德(P＜0.01),化合物CH1a、CH2a无明显促进LPS处理脾细胞的增殖(P＞0.05).CH1a、CH2a、CH1b和CH2b均可明显促进细胞因子IL-2和IL-4的增殖,与匹多莫德比较差异有统计学意义(P＜0.01).对于IFN-γ,CH1a、CH2a、匹多莫德可明显促其增殖(P＜0.01),而CH1b和CH2b对IFN-γ的增殖影响不大.结论含噻唑烷-4-酮类核苷CH1a、CH2a、 CH1b、CH2b对小鼠的免疫活性具有较好的增强作用,有可能成为潜在的免疫调节佐剂.

Study on Immunoregulation Function of Nucleoside Including Thiazolidin-4-one Ring

Objective To further illustrate the immunostimulating activity of the nucleosides containing thiazolidin-4-one ring,and evaluate the potential value as a drug.Methods The influence of thiazolidin-4-one derivates CH1a,CH2a,CH1b or CH2b on the proliferation of spleen lymphocyte treated by mitogens(ConA,LPS) was observed by cytology experiment in vitro.Using mice ELISA kit,the levels of the cytokines,such as interleukin-4(IL-4),IL-2,and interferon-γ(IFN-γ) were detected from the supernatant of cell cultures.All test indexes were compared with pidotimod.Results CH1a,CH2a,CH1b or CH2b significantly promoted proliferation of Con A-induced T cells at certain concentrations,as compared with pidotimod(P<0.01).CH1b and CH2b significantly enhanced proliferation of LPS-induced splenocytes as compared with pidotimod(P<0.01).CH1a and CH2a did not significantly increase the proliferation of LPS-induced splenocytes(P>0.05).As compared with Con A alone or pidotimod,a combination of Con A and CH1a,CH2a,CH1b or CH2b significantly increased the levels of IL-2 and IL-4 secretion(P<0.01).CH1a,CH2a and pidotimod significantly increased the secretion level of IFN-γ(P<0.01),while CH1b and CH2b had no effects on IFN-γ secretion.Conclusion The nucleoside containing thiazolidin-4-one ring(CH1a,CH2a,CH1b and CH2b) have certain activity of immunostimulating in mice and hold a potential as immunomodulators.