六味地黄丸对绝经后骨质疏松症肾阴虚证差异表达基因的影响

摘要

Objective To study the influence of Liuwei Dihuang Pills ( LDP) on differentially expressed genes in kidney Yin deficiency patients with postmenopausal osteoporosis ( POP ) .Methods Microarray was used to identify the differentially expressed genes in patients with POP kidney Yin deficiency, with kidney Yang deficiency, with no Yin deficiency, and healthy controls, in the peripheral blood.These genes were further analyzed through examination of differential gene expression patterns before and after LDP treatment.Results (1) In patients with POP kidney Yin deficiency, ASB1, CLCF1, PROK2, GPR27, and C3orf35 were down-regulated, and GSTM5 and MUC12 were up-regulated, comparing to other 3 groups.(2) After LDP treatment for 3 months, ASB1 and CLCF1 were significantly up-regulated, JAK1 and CBP were significantly down-regulated, and PROK2, GPR27, C3orf35, and GSTM5 were not change.(3) After 3-month treatment, there were 5701 differentially expressed genes, including 3072 up-regulated genes and 2629 down-regulated genes.Conclusion LDP significantly increases the expression of ASB1 and CLCF1.The potential mechanism underlying the therapeutic effect of LDP on POP kidney Yin deficiency may be related to regulation of CBP in JAK-STAT signaling pathway.%目的 探讨六味地黄丸对绝经后骨质疏松症肾阴虚证( POP)差异表达基因的影响. 方法 用基因芯片技术比较POP肾阴虚证组与POP肾阳虚证组、POP无肾虚证组、健康对照组受试者外周血基因表达谱,筛选出差异表达基因;六味地黄丸治疗POP肾阴虚证组3个月后,用基因芯片检测六味地黄丸对这些差异表达基因的影响. 结果 ①基因芯片筛选POP肾阴虚证组与其他3组比较均有显著性差异的差异表达基因:ASB1、CLCF1、PROK2、GPR27、C3orf35、GSTM5、MUC12,其中ASB1、CLCF1、PROK2、GPR27和C3orf35表达下调,GSTM5和MUC12表达上调. ②六味地黄丸治疗POP肾阴虚证组3个月后,基因芯片检测ASB1、CLCF1的表达显著上调, CLCF1参与JAK-STAT信号通路中JAK1、CBP显著下调、STAT4显著上调,而PROK2、GPR27、C3orf35和GSTM5表达水平治疗前后比较无显著性差异. ③六味地黄丸治疗POP肾阴虚证组3个月后,与治疗前相比,共有5701个差异表达基因,其中上调基因3072个,下调基因2629个. 结论 六味地黄丸上调POP肾阴虚证差异基因ASB1、CLCF1的表达,其治疗POP肾阴虚证的机理可能与其上调CLCF1介导JAK-STAT信号通路调控下游CBP表达有关.