兰州大学机构库 >学院待认领
阿霉素心肌病大鼠心肌组织部分基因表达谱的变化
Alternative Titlechanges of gene expression profile of adriamycin- induced cardiomyopaathy in rats
张升平
Thesis Advisor余静
2005-05-31
Degree Grantor兰州大学
Place of Conferral兰州
Degree Name硕士
Keyword基因芯片 阿霉素 心肌病 能量代谢 凋亡
Abstract目的:比较正常大鼠和阿霉素心肌病大鼠心肌组织中基因表达的差异,探讨阿霉素心肌病的分子生物学机制。 方法:1)建立动物模型:Wistar大鼠16只,随机分为实验组(8只),正常对照组(8只)。实验组腹腔注射阿霉素2mg/kg,每周2次;正常对照组给予腹腔注射生理盐水2ml/kg,每周2次;两组按上述剂量连续给药8周。8周后将大鼠处死,取心肌游离壁组织,电镜观察符合心肌病的病理改变特点。2)制备探针和芯片杂交:从心肌组织中抽提mRNA, 经逆转录分别用Cy3、Cy5荧光标记,获得两组动物来源的cDNA探针;cDNA探针与基因表达谱芯片杂交。3)图象检测与结果分析:杂交结果由激光扫描仪扫描并用图象分析软件进行分析、标准化处理及ratio值分析。 结果:1)共有923条基因(含未知基因和EST片段)出现差异表达,其中有586条基因表达下调,337条基因表达上调。2)能量代谢相关基因的表达水平在阿霉素心肌病时明显下调;凋亡相关基因表达水平在阿霉素心肌病时明显上调。 结论:1)凋亡和自由基损害在阿霉素心肌病的发病机制中起重要作用。2)能量代谢障碍和免疫机制紊乱加剧了病变的演变、发展。3)心肌损害是多基因复杂相互变化的综合结果,而非几个或某几组基因调控失衡。
Other AbstractObjective To observe the changes of part gene expression profiles of adriamycin cardiomyopathy rats by DNA microarray. Methods Wistar rats(n=16) were grouped randomly into a adriamycin-induced cardiomyopathy (n=8) and a normal control group(n=8). The models of adriamycin-induced cardiomyopathy in rats caused by injection of adriamycin into belly of rats were established. The cDNA probes were prepared by labeling the mRNA extracted from normal tissue and tissue of adriamycin –induced cardiomyopathy with Cy3-dUTP and Cy5-dUTP respectively through reverse transcrition. DNA microarray were constructed by spotting PCR products of 4000 rat cDNAs onto specially treated glass slides, and then hybridized against the cDNA probes followed by fluorescent signals scanning. The results were scanned and analyzed by comuputer image analysis and subjected to standardization, ratio and clustering analysis. Results Nine hundred and twenty-three genes expressed in adriamycin-induced cardiomyopathy were screened out .Five hundred and eighty-six genes were down-regulated and three hundred and thirty-seven ones were up-regulated respectively.The expression of energy metabolism-related genes were lower in the tissues of adriamycin –induced cardiomyopathy than those of normal tissue ; The expression of apoptosis-related genes were up in the tissues of adriamycin –induced cardiomyopathy than those of normal tissue. Conclusion Apoptosis and energy metabolism disorder may play an important role in the pathogenesis of adriamycin –induced cardiomyopathy.Investigation on the gene expression pattern is helpful for studying adriamycin –induced cardiomyopathy. Myocardial damage is the composite results of co-variation of multiple gene changes.
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Language中文
Document Type学位论文
Identifierhttps://ir.lzu.edu.cn/handle/262010/223856
Collection学院待认领
Affiliation临床医学院
Recommended Citation
GB/T 7714
张升平. 阿霉素心肌病大鼠心肌组织部分基因表达谱的变化[D]. 兰州. 兰州大学,2005.
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