目的 研究玄参干预对大鼠基因表达谱的影响,探讨玄参干预对大鼠的潜在保护和毒性作用及其机制.方法 将20只雄性SD(Sprague-Dawley)大鼠随机分为玄参组和空白组,每组10只.玄参组大鼠给予玄参提取物1350 mg· kg-1灌胃,空白组灌胃给予等容积0.9％氯化钠溶液,均为1次/d,连续15 d.分别于灌胃15 d后,检测肝脏组织的基因表达谱,通过时间序列趋势分析软件(Short Time-Series Expression Miner,STEM)筛选具有趋势表达的差异表达基因(differentially expressed genes,DEGs),并对其进行基因本体论(Gene Ontology,GO)功能注释和京都基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路分析.结果 玄参组筛选76个DEGs,其中28个上调,48个下调,与对照组相比,差异均具有统计学意义(P＜0.05).KEGG通路分析结果显示,丝裂原活化蛋白激酶(MAPK)、无翅型小鼠乳腺肿瘤病毒整合位点(Wingless-Type MMTV Integration Site Family,Wnt)、转化生长因子-β(Transforming growth factor-β,TGF-β)、非受体酪氨酸激酶家族-信号转导子和转录激活子(Janus Kinase-Signal Transducer and Ac-tivator of Transcription,Jak-STAT)、核因子激活的 B 细胞的 κ-轻链增强(nuclear factor kappa-B,NF-κB)、Toll 样受体(Toll-like receptor)、过氧化物酶体增殖物激活受体(peroxisome proliferator-activated receptor,PPAR)、催产 素(Oxyto-cin)、神经生长因子受体(TNFRSF16)相关蛋白 1[nerve growth factor receptor(TNFRSF16)associatedprotein 1,Ngfrap1]和神经营养因子受体相关死亡结构域(neurotrophin receptor associated death domain,Neurotrophin)这9条信号通路,包含Mecom、Amhr2、Pias2、Ticam2、Cyp7a1、Ngfrap1和Nfatc4这7个靶基因.经查阅文献,Mecom可能为表征玄参对大鼠潜在保护作用的靶基因,而另外6种则可能为表征玄参对大鼠潜在毒性作用的靶基因.结论 玄参作用的两重性,既可对机体产生预防和治疗作用,也会产生潜在的不良反应.
Study on Efficacy and Safety of Xuanshen(Radix Scrophulariae)in Rats Based on High Throughput Sequencing Technology
Objective To study the effect of Xuanshen(Radix Scrophulariae)on the gene expression profile of normal rats and discuss the potential protective and toxic effects of Xuanshen(Radix Scrophulariae)intervention on rats and its mechanism.Methods Twenty Sprague-Dawley(SD)rats were randomly divided into a control group and an aqueous extract of Xuanshen(Ra-dix Scrophulariae)group(n=10).The rats in the Xuanshen(Radix Scrophulariae)group received the aqueous extract of Xuan-shen(Radix Scrophulariae)(1350 mg of crude drug/kg)by gavage.The control group received the same volume of 0.9％Sodi-um Chloride Solution.Both groups were given the intervention once a day,continuously for 15 days.After 15 days of gavage,the gene expression profile of liver tissue was detected,and differentially expressed genes(DEGs)with trend expression were screened using Short Time Series Expression Miner(STEM)trend analysis software.Gene Ontology(GO)functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis were performed on them.Results Seventy-six DEGs were screened in the Xuanshen(Radix Scrophulariae)group,of which 28 were up-regulated(P＜0.05)and 48 were down-regulated(P＜0.05).The results of KEGG pathway analysis indicated that MAPK signaling pathway,Wnt signaling pathway,TGF-β signaling pathway,JAK stat signaling pathway,NF-κB signaling pathway,Toll like receptor signaling pathway,PPAR signaling pathway,Oxytocin signaling pathway and Neurotrophin signaling pathway were identified,including Mecom,Amhr2,Pias2,Ticam2,Cyp7a1,Ngfrap1 and Nfatc4.According to the literature review,Mecom might be the target gene to characterize the potential protective effect of Xuanshen(Radix Scrophulariae)on rats,while the other six might be the target genes for the po-tential toxic effect of Xuanshen(Radix Scrophulariae)on rats.Conclusion The duality of action of Xuanshen(Radix Scrophulari-ae)can have both preventive and therapeutic effects on the body and also can have potential side effects.
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