文献类型：期刊文献

中文题名：温补脾肾法对脾肾阳虚型UC大鼠结肠组织趋化因子信号通路的影响

英文题名：Effect of the warming and tonifying spleen-kidney method on chemokine signaling in colonic tissues of rats with spleen-kidney yang-deficiency

作者：殷银霞[1];刘永华[2];吴玉泓[2];谢守嫔[5];程小丽[2];田一虹[2];王园园[2];李海龙[3,4]

第一作者：殷银霞

机构：[1]北京中医药大学深圳医院,广东深圳518116;[2]甘肃中医药大学,兰州370000;[3]甘肃中医药大学临床医学院,兰州730000;[4]甘肃省中医方药挖掘与创新转化重点实验室,甘肃省中药药理与毒理学重点实验室,兰州730000;[5]兰州市第一人民医院,兰州730000

第一机构：北京中医药大学深圳医院,广东深圳518116

年份：2018

卷号：26

期号：5

起止页码：610

中文期刊名：中国实验动物学报

外文期刊名：Acta Laboratorium Animalis Scientia Sinica

收录：CSTPCD;;北大核心:【北大核心2017】；CSCD:【CSCD_E2017_2018】；

基金：国家自然科学基金资助项目(81260520);甘肃省高等学校科研项目资助项目(2016A-046)。

语种：中文

中文关键词：溃疡性结肠炎;特异性靶点;第二代测序;脾肾阳虚;温补脾肾;趋化因子

外文关键词：ulcerative colitis;specific target;next-generation sequencing;spleen-kidney yang-deficiency;warming and tonifying spleen-kidney;chemokine

摘要：目的寻找脾肾阳虚型UC的特异性靶点。方法 96只Wistar大鼠随机分为模型组、高剂量组、中剂量组、低剂量组、SASP组,治疗组给予相应药物灌胃治疗。分别选取空白组大鼠结肠组织与模型组大鼠病变部位结肠组织进行高通量测序。RT-qPCR法检测筛选的趋化因子的基因表达。结果与模型组大鼠相比较,根据q-value≦0.05,fold-change≧1.5筛选出空白组大鼠差异表达的基因。通过GO功能分类分析显示,差异基因功能主要富集在生物过程(biological process,BP)、细胞成分(cellular component,CC)、分子功能(molecular function,MF)三个层面。通过差异基因KEGG富集分析发现趋化因子信号通路中CXCL1、CXCL2、CXCR2、CXCL6、CCL7、CCL12基因表达显著上调;并通过RT-qPCR法验证,以上因子的基因表达变化与测序结果一致,经温补脾肾方药治疗后,以上因子表达明显下调。结论脾肾阳虚型溃疡性结肠炎趋化因子信号通路中CXCL1、CXCL2、CXCR2、CXCL6、CCL7、CCL12基因表达显著上调,可作为UC黏膜炎症活动的客观指标。具有温补脾肾作用的理中汤合四神丸复方中药颗粒可以有效下调以上因子的表达,减缓炎症反应,促进受损伤的结肠黏膜的修复。
Objective To determine the specific targets for spleen-kidney yang-deficiency ulcerative colitis(UC).Methods Ninety-six Wistar rats were randomly divided into the model,high dose,middle dose,and low dose sulfasalazine(SASP)groups.Then,next-generation sequencing was performed on colon lesions from the blank and model groups.Real-time quantitative PCR was performed to detect the mRNA expression of screened chemokines.Results Compared with the model group,differentially expressed genes in the blank group were screened according to a q-value of 0.05 and fold-change of 1.5.According to Gene Ontology classification analysis,the differentially expressed genes mainly functioned in three pathways:biological process,cellular component,and molecular function.Kyoto Encyclopedia of Genes and Genomes enrichment analysis of the differentially expressed genes showed alterations in the chemokine signaling pathway,and real-time quantitative PCR confirmed that CXCL1,CXCL2,CXCR2,CXCL6,CCL7,CCL12,and CCL7 were significantly unregulated.Thus,the expression of the above factors was consistent with sequencing,and levels of these factors were decreased following treatment.Conclusions CCL12 expression was significantly unregulated along with the chemokine signaling pathway involving CXCL1,CXCL2,CXCR2,CXCL6,CCL7,and CCL12 in spleen-kidney yang-deficiency UC.Thus,this panel can be used as an objective index of inflammation for UC mucosa.Warming the spleen and kidney with Lizhong decoction and Sishen pills can effectively downregulate the expression of these factors,which restrained inflammatory reactions and promoted the repair of injured colonic mucosa.