摘要
目的探究胰岛淀粉样多肽(IAPP)治疗阿尔茨海默病(AD)小鼠的脑组织环状RNA(circRNA)和信使RNA(mRNA)表达谱变化及分子机制。方法将6只APP/PS1小鼠按随机数字表法随机分为IAPP干预组和参照组,每组3只。干预组小鼠腹腔注射0.5μmol/L的IAPP(200μg/kg),参照组小鼠注射相同剂量的磷酸缓冲盐溶液。使用基因芯片技术检测2组小鼠之间差异表达的circRNAs和mRNAs,通过qRT-PCR对芯片结果进行验证,并对差异表达的mRNAs进行GO和KEGG通路分析。结果按照差异倍数的绝对值(|FC|)≥1.5且P<0.05的筛选标准,IAPP干预组与参照组之间有899个差异表达circRNAs,343个上调和556个下调,差异表达mRNAs有2257个,1310个上调和947个下调。qRT-PCR验证结果均与芯片结果一致。GO分析显示,差异表达mRNAs主要富集于G蛋白偶联受体、细胞代谢等生物功能;KEGG通路分析显示,差异表达mRNAs主要与柠檬酸循环、蛋白酶体、IL-17和趋化因子信号通路等相关。结论腹腔注射IAPP后AD小鼠脑组织中circRNAs和mRNAs表达谱发生显著变化,提示这些差异表达的circRNAs和mRNAs可能是IAPP治疗AD小鼠的关键机制。
Objective To investigate the changes of circulating RNA(circRNA)and messenger RNA(mRNA)expression profiles in brain tissue of mice with Alzheimer's disease(AD)treated with islet amyloid polypeptide(IAPP)and the molecular mechanisms.Methods According to the number table method,6 APP/PS1 mice were randomly divided into IAPP intervention group and reference group,3 mice in each group.The intervention group mice were injected intraperitoneally with 0.5μmol/L of IAPP(200μg/kg),the reference group mice were injected with the same dose of phosphate buffer saline.Differentially expressed circRNAs and mRNAs between the two groups of mice were detected using gene chip technology.Chip results were validated by qRT-PCR.Differentially expressed mRNAs were analyzed by GO and KEGG pathways.Results According to the screening criteria of difference fold change(|FC|)≥1.5 and P<0.05,there were 899 differentially expressed circRNAs,343 up-regulated and 556 down-regulated,and 2257 differentially expressed mRNAs,1310 up-regulated and 947 down-regulated,between the IAPP intervention group and the reference group.qRT-PCR validation results were consistent with the gene chip results.GO analysis showed that the differentially expressed mRNAs were mainly enriched in G protein-coupled receptor,cell metabolism and other biological functions.KEGG pathway analysis showed that they were mainly involved in citrate cycle,proteasome,IL-17 and chemokine signaling pathway,etc.Conclusion The expression profiles of circRNAs and mRNAs in the brain tissue of AD mice were significantly changed after intraperitoneal injection of IAPP,suggesting that these differentially expressed circRNAs and mRNAs may be the key mechanisms of IAPP treatment in AD mice.
作者
李小雄
李金平
黄洁
马晶晶
侯明亮
马琳秋
王从过
周华东
LI Xiaoxiong;LI Jinping;HUANG Jie;MA Jingjing;HOU Mingliang;MA Linqiu;WANG Congguo;ZHOU Huadong(Departments of Neurology,the First Affiliated Hospital of Bengbu Medical College,Bengbu,Anhui 233004,China)
出处
《中华全科医学》
2023年第7期1101-1104,共4页
Chinese Journal of General Practice
基金
国家自然科学基金项目(81771177)。
