清开灵有效组分药理通路的多样性分析

Differences in pharmacological pathways among Qingkailing effective component

目的比较清开灵有效组分BA(黄芩苷)、JA(栀子苷)、CA(胆酸)与CM(珍珠母)在治疗脑缺血过程中药理通路变化机制。方法将脑缺血模型小鼠随机分为BA、JA、CA、CM和M(模型组),每组15只,脑缺血后2h予以相应药物治疗,24h后断头取脑,抽提小鼠脑海马组织的总RNA,利用与脑缺血相关的374个基因的cDNA芯片检测基因表达谱变化。将所有数据标准化处理后,以Arraytrack软件为平台,选取BA与M,JA与M,CA与M和CM与M两组间t检验得出的差异基因(P<0.05,Foldchange>1.5),将差异表达基因按照Genebank ID上传到GeneGo数据库,选取P<0.05的信号通路,选取各组分P值最小的前2位药理通路分析不同组分的药效机制。结果BA、JA、CA、CM与M组比较后差异基因数量分别为46、50、54和30条,根据这4个组分差异基因相似度最大的前2位信号通路可看出JA、CA、CM都参与凋亡与存活-TNFR1信号通路的调控,另外BA表现为对G蛋白信号和A2A受体信号的调控作用,CA表现为调节NMDA依赖性的LTP的调节。结论清开灵组分发挥药效作用具有多样性特点,BA主要表现为抗凋亡,JA主要表现为抑制细胞凋亡和促进缺血后脑保护等方面,CA侧重于抑制钙离子内流,抗神经元变异方面,但CM效果不甚理想。

Aim Purpose-The aim of this study is utilizing the highthrough genechip data to Compare the difference of the pharmacological pathways among the Qingkailing effective components Baicalin（BA）,Jasminoidin（JA）,cholic acid（CA） and Concha margaritiferausta（CM）in the treatment process of cerebral ischemia.Methods The focal cerebral ischemia-reperfusion model mice were randomly divided into groups of Baicalin（BA）,Jasminoidin（JA）,cholic acid（CA）,Concha margaritiferausta（CM）and model group（M）,15 mice for each group,24 hours later total RNA were abstracted from the hippocampus,we selected 374 gene expression profile related to cerebral ischemia,made cDNA chip marked by Cy3/Cy5,detect the variation of different components,Then apply Arraytrack software to select differentiate expressed genes between BA and M,JA and M,CA and M,CM and M by T-tests,select genes with P〈0.05,Fold change〉1.5,according GeneGO software to find the top two pathways of each components.Results the number of differentiate expressed genes between BA,JA,CA,CM and M is separately 46,50,54 and 30,according to the top two pathways of GeneGo display JA,CA,CM all participate Apoptosis and survival_TNFR1 signaling pathway,besides BA participate in regulating G-protein signaling and Development_A2A receptor signaling while CA in Neurophysiological process_NMDA-dependent postsynaptic long-term potentiation in CA1 hippocampal.Conclusion Qingkailing effective components take diversity Pharmacological characteristics,BA mainly for anti-apoptosis,JA mainly for inhibit apoptosis and promote ischemic brain protection,etc,CA focused on inhibiting calcium influx,and anti-neuron variability.But CM has no good results on this.