基因芯片筛选电针预处理心肌缺血再灌注大鼠细胞色素P450代谢通路相关差异表达基因  

Differential Expressed Genes of Cytochrome P450 Metabolic Pathway in Electroacupuncture Preconditioning on Myocardial Ischemia/Reperfusion Rats Screened by Microarray Technology

作　　者：李洋[1] 邵明璐[1] 杨琳[1] 谭奇纹[2] 崔华峰[3] 

机构地区：[1]山东中医药大学,山东济南250011 [2]山东中医药大学针灸推拿学院,山东济南250011 [3]山东中医药大学附属医院针灸科,山东济南250011

出　　处：《辽宁中医杂志》2017年第4期691-694,I0002,共5页Liaoning Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金(81373722);山东省自然科学基金联合专项(ZR2014HL100)

摘　　要：目的:利用基因芯片技术筛选电针预处理心肌缺血再灌注(MIR)大鼠心肌组织中细胞色素P450代谢通路相关差异表达的基因,寻找电针预处理对MIR大鼠产生保护作用的可能发生机制。方法:72只成年Wistar大鼠,雌雄各半,随机分为假手术组(Sham)、模型组(IR)、夹脊组(JJ)、内关组(NG)、阳陵泉组(YLQ)、曲池组(QC),每组12只。电针预处理组每天针刺30 min,连续针刺7 d。采用结扎左冠状动脉前降支的方法复制心肌缺血再灌注损伤模型。提取心肌组织总RNA并进行评估,根据Agilent One-Color Microarray-Based Gene Expression Analysis实验方案进行样品标记和芯片杂交,使用Agilent Feature Extraction、Gene Spring GX v12.1进行数据处理,使用标准的富集计算方法进行GO分析和Pathway分析。结果:电针预处理能够调控缺血再灌注大鼠的基因表达,其中夹脊穴组和内关穴组对细胞色素P450代谢通路相关基因影响显著,上调CYP450表氧化酶基因Cyp2b3、Cyp2c11、Cyp2b2、Cyp2s1,同时下调ω-羟化酶基因Cyp4a2、Cyp1a1、Cyp1b1,阳陵泉组和曲池组无显著性差异。结论:多个基因参与心肌缺血再灌注过程,涉及多条信号通路,电针夹脊穴和内关穴能够上调CYP2家族基因,下调CYP1和CYP4家族基因,从分子水平阐明了其对MIRI的保护作用机制。Objective ： To screen differential expressed genes of cytochrome P450 metabolic pathway in electroacupuncture pre- conditioning on the myocardial ischemia/reperfusion rats by microarray and found the possible mechanisms of lectroacupuncture＇s protective effects. Methods ： Seventy - two adult wistar rats were randomly divided into model group （ IR）, sham operation group （Sham）, Jiaji group （ JJ ）, Neiguan （ PC6 ） group （ NG ）, Yanglingquan （ GB34 ） group （ YLQ ）, Quchi （ LI11 ） group （ QC ）, 12 in each group. The rats in the treatment groups were treated with electroacupuncture for 30 rain, once a day for seven days. By liga- ting the left anterior descending coronary artery to copy the myocardial ischemia - reperfusion injury model. Total RNA was extrac- ted from myocardial tissue and evaluated, labeled and microarray hybridized according to the protocol Agilent One - Color Mi- croarray- Based Gene Expression Analysis ,Agilent Feature Extraction software and GeneSpring GX v12.1 software package were used to data processing. GO analysis and Pathway analysis were performed in the standard enrichment computation method. Re- sults ： Electroacupuncture preconditioning can regulate gene expression in rat ischemia - reperfusion, genes on cytochrome P450 metabolic pathways can be significantly regulated by Jiaji group and Neiguan （PC6） group, the epoxygenase such as Cyp2b3, Cyp2cl 1, Cyp2b2, Cyp2sl can be up- regulated,while the w- hydroxylase genes such as Cyp4a2, Cyplal, Cyplbl can be down -regulated. The Yanglingquan（GB34） group and Quchi（ LIll ） group had no significant difference. Conclusion： Multiple genes were involved in myocardial ischemia and reperfusion process, involving multiple signaling pathways, Jiaji and Neiguan（PC6） can up - regulate CYP2 family genes, and down - regulate CYP1 CYP4 family genes, thus elucidating the protection mechanisms from the molecular level.

关 键 词：基因芯片技术 电针预处理 心肌缺血再灌注 细胞色素P450代谢通路 

分 类 号：R285[医药卫生—中药学]