基于转录组学探讨白芍调控细胞因子免疫调节的作用机制OACHSSCD

Objective:To investigate the ameliorative effects of Paeoniae Radix Alba on immunosuppressed mice and its potential mechanisms.Methods:Ninety male Kunming(KM)mice were randomly divided into a blank group,model group,ginseng group(0.5 g/kg),and low-,medium-,and high-dose groups of Paeoniae Radix Alba aqueous extract(463.3,926.7,and 1 390.0 mg/kg,respectively)according to a random number table,with continuous administration for 30 days.An immunosuppressed mouse model was established by intraperitoneal injection of cyclophosphamide(80 mg/kg)on days 12 and 13.Body weight,spleen index,thymus index,splenic lymphocyte transformation,NK cell activity,serum immunoglobulin G and M(IgG,IgM),and complement components 3 and 4(C3,C4)were measured.Differentially expressed genes were identified by transcriptome sequencing and sub-jected to enrichment analysis,and key targets were validated by real-time quantitative PCR(RT-qPCR)and Western blot(WB).Results:Compared with the blank group,the model group showed decreased body weight on day 30,reduced thymus and spleen in-dices,decreased lymphocyte transformation,NK cell activity,and reduced levels of IgG,IgM,C3,and C4(P＜0.05).Compared with the model group,these indices were increased in all treatment groups(P＜0.05).Transcriptome sequencing revealed that the cytokine-cytokine receptor interaction pathway was a key signaling pathway.Interleukin-1 receptor-like 1(IL1RL1),tumor necrosis factor ligand superfamily member 12(TNFSF12),chemokine(C-C motif)ligand 24(CCL24),and interleukin-2 receptor subunit beta(IL2RB)were identified as key targets.Compared with the blank group,the model group showed increased IL1RL1 mRNA and protein expression and TNFSF12 mRNA expression,and decreased IL2RB mRNA and protein expression(P＜0.05).Compared with the model group,the high-dose Paeoniae Radix Alba aqueous extract group showed decreased IL1RL1 mRNA and protein ex-pression and TNFSF12 mRNA expression,and increased IL2RB mRNA and protein expression(P＜0.05).Conclusion:Paeoniae Radix Alba exerts immunoprotective effects in immunosuppressed mice.Its immunoregulatory mechanism is associated with modula-tion of IL1RL1,TNFSF12,and IL2RB expression and regulation of the cytokine-cytokine receptor interaction pathway.