钙离子信号通路对肾虚型阿尔茨海默病作用机制转录组学研究

Transcriptional Study on Mechanism of Ca^2+Signaling Pathway on Alzheimer’s Disease of Kidney Deficiency Type

目的针对肾虚型阿尔茨海默病小鼠与对照组小鼠的对比转录组学研究,分析肾虚型阿尔茨海默病小鼠病理机制相关通路及基因差异表达情况,探讨相关病理机制。方法设置正常组与肾虚阿尔茨海默病模型组,Illumina Hi Seq TM平台检测模型组小鼠基因转录组学差异表达,通过功能注释以及富集分析模型组小鼠基因测序情况,筛选出与肾虚阿尔茨海默病病理机制相关的基因以及代谢途径。根据转录组学结果,采用Real-time PCR方法对参与病理机制形成的信号通路中差异表达基因进行量化。结果通过GO、KEGG富集结果分析,肾虚阿尔茨海默病病理机制主要涉及ECM-receptor interaction、Protein digestion and absorption、Pancreatic secretion、Calcium signaling pathway、Cell adon molecules等信号途径。肾虚型阿尔茨海默病模型组对比对照组差异基因一共1765个,其中肾虚阿尔茨海默病组1219个基因表达上调,546个基因表达下调;Real-time PCR法对致病小鼠海马转录组数据库关键基因进行转录丰度验证结果显示,钙离子信号通路中Camk2a、IP3R、Calm13个基因在小鼠海马组织中均有表达,且表达量比值趋势与转录组表达趋势一致。结论通过对肾虚阿尔茨海默病小鼠的转录组学研究结果及Real-time PCR验证分析,肾虚阿尔茨海默病涉及的病理机制较多,肾虚阿尔茨海默病模型组小鼠海马神经元内Camk2a表达下调,IP3R、Calm1表达上调,可以说明肾虚阿尔茨海默病的病理机制可能与钙离子信号通路表达异常有关。

Objective To analyze the pathological pathway and gene differential expression of Alzheimer’s disease mice with kidney deficiency type and explore the related pathological mechanism of Alzheimer’s disease mice with kidney deficiency and analyze the pathophysiological pathway and gene differential expression of Alzheimer’s disease mice with kidney deficiency.Methods The normal group and the Alzheimer’s disease with kidney deficiency model group were set up,and the Illumina Hi Seq TM platform was used to detect the differential expression of gene transcriptome in the model group.Based on transcriptome results,the differentially expressed genes in signaling pathways involved in pathological mechanism formation were quantified using real-time PCR.Results Through the analysis of GO and KEGG enrichment results,the pathological mechanism of Alzheimer’s disease with kidney deficiency was mainly related to ECM-receptor interaction,Protein digestion and absorption,Pancreatic secretion,Calcium signaling pathway,Cell adon molecules and other signaling pathways.Compared with the normal group,there were 1765 differentially expressed genes in the Alzheimer’s disease with kidney deficiency model group,of which there were 1765 genes.The expressions of 1219 genes in Alzheimer’s disease with kidney deficiency model group were up-regulated and 546 genes were down-regulated.The transcriptional abundance of key genes in Alzheimer’s disease with kidney deficiency model group was verified by Real-time PCR method.The results showed that all Camk2 a,IP3 R and Calm13 genes in calcium signaling pathway were expressed in hippocampal tissue of mice,and the trend of expression ratio was consistent with that of transcriptional group.Conclusion Through the results of transcription histology and Real-time PCR verification analysis of Alzheimer’s disease mice with kidney deficiency,there are many pathological mechanisms involved in Alzheimer’s disease with kidney deficiency.The expression of Camk2a in hippocampal neurons of Alzheimer’s disease mice with kidney deficiency is down-regulated and the expressions of IP3R and Calm1 are up-regulated,indicating that the pathological mechanism of Alzheimer’s disease may be related to the abnormal expression of calcium signaling pathway.