| 张冬梅,吴爱明,娄利霞,赵明镜,王硕仁.心肌梗死后心力衰竭模型大鼠离子通道基因表达谱的变化[J].,2010,30(1):53-57 |
| 心肌梗死后心力衰竭模型大鼠离子通道基因表达谱的变化 |
| Alteration of Ion Channel Gene Expression Profile in Rat Model of Post-myocardial Infarction Heart Failure |
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| DOI： |
| 中文关键词: 心肌梗死后心力衰竭 基因芯片 离子通道 |
| 英文关键词:post-myocardial infarction heart failure gene chip ion channel |
| 基金项目:国家自然科学基金资助项目(No.30672754) |
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| 中文摘要: |
| 目的为研究心肌梗死后心力衰竭发生、发展相关的离子通道基因,进行心肌梗死后心力衰竭模型大鼠非梗死区心肌组织和正常大鼠心肌组织基因的差异表达,及其生物信息学Stc-GO分析。方法健康雄性SD大鼠行左冠状动脉结扎术造成心肌梗死后心力衰竭模型,假手术组只穿线不结扎,每组6只。分别于心力衰竭形成期(术后10天)和稳定期(8周)取材,每组3只。取大鼠左心室非梗塞区和假手术组左心室心肌组织,进行总RNA抽提,逆转录制备探针,与双通道cDNA大鼠离子通道基因表达谱芯片进行杂交,杂交后信号经扫描仪检测,计算机分析筛选心肌梗死后心力衰竭发生发展的相关差异表达基因。并对所得结果进行Stc-GO功能集群分析,研究该类表达趋势中具有显著性意义的Gene Ontology(GO)分类。结果按差异显著性标准,从746条基因中筛选出在急性心肌梗死后心力衰竭10天大鼠的左心室非梗塞区中共同差异表达基因319条,均为上调表达。心肌梗死后心力衰竭8周大鼠的左心室非梗塞区中共同差异表达基因276条,其中上调表达的基因有274条,下调表达的基因有2条。对这些差异表达的基因进行了初步分类,表达上调的基因包括各类激素受体、细胞因子受体、神经激素受体、生长因子受体、核受体、蛋白磷酸化酶、G蛋白、配体或电压介导的各种离子通道、转运蛋白、受体干扰蛋白等,表达下调的基因包括钾通道、转运蛋白等。进一步的Stc-GO分析发现,肾上腺能受体激酶β1(βARK1)、盐酸阿米洛利敏感阳离子通道-2(Accn2)、电压依赖性钙离子通道γ亚基-1(Cacng1)、环核苷酸门控通道-α1(Cnga1)、谷氨酸盐受体海人藻酸2(Grik2),神经酪氨酸激酶受体-2(Ntrk2)等6条基因不但在模型组与假手术组相比时是显著性的上调差异基因,而且都随着时间的延长而呈下调趋势。经RT-PCR实验,有4条基因获得验证。结论Accn2、Grik2、Ntrk2、Cacng1在急性心肌梗死后心力衰竭中表达上调,其作用机制有待进一步研究。 |
| 英文摘要: |
| Objective To investigate the ion channel genes related with the genesis and development of heart failure after myocardial infarction through analyzing the differential gene expressions in non-infarcted myocardial tissues of post-myocardial infarction heart failure(PIHF) rat model,and that of normal rat,and the bio-informatic Stc-GO analysis on them.Methods Rat model of PIHF was established by left anterior descending coronary artery ligation in six SD rats,and a control group with six sham-operative rats was set.Myocardial samples were taken in two batches from them(three rats in each group) at the heart failure formation stage and the stable stage(10 days and 8 weeks after operation) respectively.Total RNA extraction,probe preparation with reverse transcription,hybridization with double-channel cDNA microarray of rat’s ion channel genes,and computerized differential gene expression screening were conducted,and Stc-GO functional clustering analysis was performed on the outcomes obtained to search out the GO sort of significance in them.Results At 10 days after operation, 319 common differential expressed genes were found from the 746 target genes,all of them were up-regulated. At 8 weeks after operation,in the 276 differential expressed genes,274 were up-regulated while the other two down-regulated.The up-regulated genes were those concerning receptors of various hormones,cytokines,neu- ro-homones,growth factors and nuclear receptor,protein phosphrylase,G protein,various ion channels mediated by ligand or voltage,transport protein,receptor interfering protein,etc.The down-regulated genes concerning the potassium channel and transport protein,etc.Stc-GO analysis found that the six genes concerning adrenergic receptor kinase beta 1(βARK1),amiloride-sensitive cation channel 2 neuronal(Accn2),voltage-dependent calcium ion channelγsubunit 1(Cacng1),cyclic nucleotide gated channel alpha 1(Cnga1),Glutamate receptor ionotropic kainite 2(Grik 2) and neurotrophic tyrosine kinase receptor type 2(Ntrk 2),were all the significantly up-regulated differential genes of the model group related with the sham-operative group,and all showed a down-regulating trend as time goes on,and four genes in them were validated by the RT-PCR test. Conclusion Ion channel genes concerning Accn2,Grik2,Ntrk2 and Cacng1 were up-regulated in PIHF,and its mechanism is waiting for further study. |
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