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作 者:王萧[1] 许庆文[2] 董浩然[1] 陈嘉[1] 陈苑[1]
机构地区:[1]广州中医药大学实验动物中心,广州510405 [2]广州中医药大学临床药理所,广州510405
出 处:《中药新药与临床药理》2012年第4期386-390,共5页Traditional Chinese Drug Research and Clinical Pharmacology
基 金:广东省自然科学基金(8151040701000001);广东省中医治法与中药创制实验室子课题(AAF302111A46)
摘 要:目的通过观察cAMP、cGMP的含量和比值,以及对基因表达谱芯片的分析,从微观角度揭示家兔心气虚证心衰模型的发病机制。方法导管术造成家兔充血性心力衰竭,于15 d、30 d取血检测cAMP、cGMP含量并剪取心肌组织进行HE染色及病理观测损伤程度,并利用全基因表达谱芯片分析心气虚型心衰模型家兔的基因表达差异。结果①正常家兔的心肌细胞无损伤,造模15 d、30 d家兔均出现心肌细胞损伤,且30 d的损伤更加广泛和严重;②与正常对照组比较,造模15 d和30 d组cGMP含量增加(P<0.05),cAMP含量和cAMP/cGMP比值下降(P<0.05),且30 d组与15 d组比较cGMP含量增加(P<0.05),cAMP含量和cAMP/cGMP比值下降(P<0.05);③15 d、30 d模型组与正常对照组间差异基因的交集基因有665个,对NCBI中功能注释明确的家兔基因,应用序列比对来注释功能,得到16个功能明确的基因,它们主要与离子通道、肌收缩和信号转导等功能有关。结论血清cAMP、cGMP含量、cAMP/cGMP比值可较好地反映心气虚证家兔心衰的病变程度,可用于对该模型进行评价;交集的665个基因包含模型稳定影响的基因,对该部分基因进行分析挖掘有望找到受模型影响的特异基因。Objective The contents of cAMP and cGMP and their ratio as well as their gene expression profiles were investigated for the exploration of pathogenesis of heart-qi deficiency heart failure in rabbit models. Methods The rabbit model with congestive heart failure was set up by catheterization. On day 15 and 30 of the experiment, serum cAMP and cGMP contents were detected, myocardial pathological damage was examined after HE staining and the differences of expression profiles were investigated with overall gene expression profile clips in heart-qi deficiency heart failure rabbits. Results (1)Normal rabbits had no damage in myocardial cells, but myocardial damage occurred in the model rabbits on day 15 and 30 of the experiment, and was severer on day 30.(2)Compared with the normal group, the content of cGMP increased(P 〈 0.05), the content of cAMP and the ratio of cAMP / cGMP decreased(P 〈 0.05) in the 15-day model group and 30-day model group. Compared with the 15-day model group, the content of cGMP increased(P 〈 0.05), the content of cAMP and the ratio of cAMP / cGMP decreased(P 〈 0.05) in the 30-day model group. (3)There were 665 intersection genes between the model rabbits and normal rabbits on day 15 and 30. Function annotation was executed by sequence alignment for the rabbit genes with definite NCBI note, and then 16 genes were found being related to the function of ion channel, muscle contraction and signal transduction. Conclusion The serum contents of cAMP and cGMP as well as their ratio were sensitive indexes of the heart failure rabbits with heart-qi deficiency, which reflect the injury of myocardial cells definitely. The 665 intersection genes include the sta- ble genes which are specific for the heart failure model.
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