雷公藤内酯醇抑制外周血单个核细胞分泌IL-10与IL-10基因-592A/C多态性相关

Inhibitory effect of triptolide on interleukin-10 production from peripheral blood mononuclear cells is associated with interleukin-10 gene-592A/C polymorphism

目的探讨雷公藤内酯醇对体外培养的外周血单个核细胞(peripheralbloodmononucle-arcells,PBMC)分泌白细胞介素-10(interleukin-10,IL-10)的抑制作用与IL-10基因592位点A/C多态性的关系。方法采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法对32名健康志愿者IL-10基因启动子区592位点A/C多态性进行基因型检测,同时进行PBMC培养,用脂多糖(lipopolysaccharidc,LPS)刺激培养细胞,并予以雷公藤内酯醇处理PBMC,收集培养上清液,酶联免疫吸附试验(ELISA)法检测上清液中IL-10的含量。结果AA基因型15名,非AA基因型17名。两组不同基因型PBMC经LPS刺激后培养上清液中IL-10水平差异无统计学意义,但有非AA基因型高于AA基因型的趋势。雷公藤内酯醇能显著抑制LPS诱导的PBMC分泌IL-10(P<0.01),并且其对携带IL-10基因-592位点非AA基因型PBMC分泌IL-10的抑制率显著高于携带AA基因型者(P<0.05)。结论雷公藤内酯醇对携带IL-10基因592位点A/C不同基因型的PBMC分泌IL-10的抑制作用差异有统计学意义,对携带非AA纯合子基因型者抑制作用较强,这可能是导致雷公藤药理作用出现个体差异的原因之一。

Objcctivc To explore whether the inhibitory effect of triptolide on intedeukin-lO （IL-1O） secretion by peripheral blood mononuelear cells （PBMC） is associated with IL-1O gene-592 A/C polymorphism. Methods IL-1O gene-592 A/C polymorphism was analyzed in 32 healthy volunteers by PCR-RFLP Meanwhile IL-IO was also measured in the supematant of the cuhured and stimulated PBMC by ELISA. Resuits＇ In 32 suhjects, 15 were A/A genotype, 17 subjects were non-A/A genotype. There was a tendency that the secretion level of IL-1O in non-AA group was higher than in AA group after LPS stimulation in PBMC cultures of healthy subjects, but there was not a statistical significance between the two groups. Triptolide suppressed the production of IL-1O significantly in LPS-treated human PBMC （P〈O.O1）. Furthermore, stronger suppressive effect was found in PBMC carried non-A/A genetype than in PBMC carried A/A genetype （P〈O.05）. Conclusion The inhibitory effect of triptolide on the prnduetion of IL-1O is different between A/A and non- A/A genetype of IL-10-592 （stronger in non-A/A genotype）, which may be one of the reasons for Ihe phenomenon that patients respond to triptolide differently.