甘肃黄芪对多柔比星心肌病大鼠心肌组织部分基因表达的影响

 目的比较正常大鼠和多柔比星心肌病大鼠心肌组织部分基因表达谱的差异,探讨甘肃黄芪对上述基因表达谱的影响。方法30只Wistar大鼠随机分3组:对照组即生理盐水组(n=10),多柔比星组(n=10)和黄芪+多柔比星组(n=10)。分别从3组心肌组织中抽提总RNA,用Cy3,Cy5荧光标记,经逆转录合成动物来源的cDNA探针;cDNA探针与4000点基因表达谱芯片杂交,结果由软件分析表达信号。结果共有923条基因出现差异表达,其中586条基因表达下调,337条基因表达上调。凋亡相关基因表达在多柔比星心肌病时上调;氧化和能量代谢相关基因的表达在多柔比星心肌病时下调。6个在多柔比星组上调的基因在黄芪+多柔比星组下调,8个在多柔比星组下调的基因在黄芪+多柔比星组上调,3个在多柔比星组上调的基因在黄芪+多柔比星组表达进一步增强。结论凋亡和能量代谢障碍及免疫因素在多柔比星心肌病的发病机制中参与作用,甘肃黄芪对多柔比星诱导的心肌病大鼠的心脏保护作用是通过多基因多途径调节相关基因表达而实现的。

Effect of Radix Astragali Gansuensis on Genetic Expression Spectra in Myocardium of Rats with Doxorubicin-Induced Cardiomyopathy

OBJECTIVE To investigate the difference of genetic expression spectra between doxorubicin-induced cardiomyopathy in rats and normal controls by DNA microarray.To explore the effects of Radix Astragali Gansuensis on gene expression profiles in rats with doxorubicin-induced cardiomyopathy.METHODS Thirty Wistar rats were divided randomly into 3 groups,i.e control group2(n=10),doxorubicin group(n=10) and Radix Astragali doxorubicin group(n=10).cDNA probes were prepared by labeling the mRNA extracted from myocardium and marked with Cy3-dTP and Cy5-dUTP respectively through reverse transcrition.DNA microarray were constructed by spotting PCR products of 4 000 and cDNAs onto specially treated glass slides and were then hybridized against the cDNA probes followed by fluorescent signals scanning.RESULTS Nine hundred and twenty three genes were detected with differential expressions.The expressions of 586 genes were found to be down-regulated and 337 ones up-regulated.Energy metabolism-related genetic expressions were down-regulated in tissues of rats with doxorubicin-induced cardiomyopathy compared with normal tissue.Expressions of apoptosis-related genes were up-regulated in tissues of doxorubicin-induced cardiomyopathy.Six up-regulated and 8 down-regulated genes in doxorubicin group were down-regulated and up-regulated in Radix Astragali doxorubicin group respectively.Expressions of 3 up-regulated genes in doxorubicin group were further enhanced in Radix Astragali doxorubicin group.CONCLUSION Apoptosis,energy metabolism disorder and immunity may participate the pathogenesis changes in rats with doxorubicin-induced cardiomyopathy.Radix Astragali Gansuensis can protect the heart in rats with doxorubicin-induced cardiomyopathy.Multiple gene expressions are involved to implement this pharmacological effect.