心肌梗死后心力衰竭大鼠心脏基因表达谱及活血益气方药对其心脏的影响

目的 观察活血益气方药对心肌梗死后心力衰竭模型大鼠心脏功能结构的影响。方法 以大鼠左冠状动脉结扎术造成心肌梗死后心衰模型。对心衰形成期(术后10天)、稳定期(术后8周)大鼠左心室梗死区、非梗死区和同期假手术组左心室分别取材并提取总RNA，以6张大鼠40S基因芯片(4096个基因／张芯片)对其进行检测；用基因芯片分析软件Genespring、Treeview、Clustering、SOM对芯片结果进行分析、术后4周以活血益气方药对模型大鼠开始治疗，共4周，以卡托普利作为阳性对照药；经阻抗法观察给药前后大鼠心脏功能和心脏系数的变化。结果 (1)用Genespring软件分析基因表达谱芯片检测结果发现有参与能量代谢、心肌细胞骨架及纤维化等13类共千余条表达显著上调和下调的基因，在梗死区差异表达基因以形成期最多(1086条)、稳定期次之(724条)；而非梗死区差异表达基因也以形成期最多(196务)，稳定期较少(97条)。(2)心肌梗死后心衰大鼠经活血益气方药、卡托普利治疗，心功能明显改善，每搏输出量(SV)、心输出量(CO)、心脏指数(CI)均较治疗前显著提高(P<0．01)；同时活血益气方药还能改善模型动物的心脏系数(与模型组比较，P<0．01，与假手术组比较，P>0．05)。结论 心肌梗死后心衰是一种多基因表达异常的超负荷心脏病，活血益气方药能改善心肌梗死后心衰大鼠心脏功能和组织学指标，达到治疗心衰的作用。

Study on Cardiac Gene Expression Microarray and Recipe for Activating Blood Circulation and Supplementing Qi on Heart of Rats with Post infarction Heart Failure

OBJECTIVE: To observe the effect of recipe for activating blood circulation and supplementing Qi (RAS) on cardiac functional structure in rats with post-infarction heart failure (PIHF). METHODS: Rat model of PIHF was established by left coronary artery ligation. Left ventricular samples of model rats from infarcted or peri-infarcted area were obtained at PIHF formation stage and stable stage (10 days and 8 weeks respectively after operation), the total RNA extracted and detected using 6 pieces of rat's 40s gene microarray (4096 genes/microarray), the data were analyzed using software as Genespring, Treeview, Clustering and SOM. Besides, RAS was used to treat the model rats beginning from 4 weeks after modeling and lasted for 4 weeks, changes of heart function and cardiac coefficient before and after treatment were observed by impedance method with Captopril as positive control. RESULTS: (1) Genespring analysis showed thousands of genes differential expression (upper or down regulated), including 13 kinds of gene involving energy metabolism, myocardial cytoskeleton, fibrosis, etc. which, in the infarcted area at heart formation stage were 1086 genes and at the stable stage, 724 genes, while in the peri-infarcted area, formation stage 196 genes and stable stage 97 genes. (2) After RAS or Captopril treatment, the heart function improved significantly, with the stroke volume, cardiac output and cardiac index increased significantly (P < 0.01). RAS could also improve the cardiac coefficient of model rats, as compared with that in untreated model, P < 0.01, compared with that in the sham-operated rats, P < 0.05. CONCLUSION: PIHF is a kind of overload heart disease with multiple genes abnormality. RAS could improve the heart function and histologic indexes, so as to treat the heart failure.