Background: Based on global gene expression profile,
therapeutic effects of
Qishenyiqi (QSYQ) on acute
myocardial infarction (AMI) were investigated by integrated analysis at multiple levels including gene expression, pathways involved and functional group. Methods: Sprague-Dawley (SD) rats were randomly divided into 3 groups:
Sham-operated, AMI model (left anterior descending coronary artery
ligation) and QSYQ-treated group. Cardiac tissues were obtained for analysing digital gene expression. Sequencing and transcriptome analyses were performed collaboratively, including analyses of differential gene expression, gene co-expression network, targeted attack on network and functional grouping. In this study, a new strategy known as keystone gene-based group significance analysis was also developed. Results: Analysis of top keystone QSYQ-regulated genes indicated that QSYQ ameliorated
ventricular remodeling (VR), which is an irreversible process in the pathophysiology of AMI. At pathway level, both well-known
cardiovascular diseases and cardiac signaling pathways were enriched. The most remarkable finding was the novel
therapeutic effects identified from functional group analysis. This included anti-inflammatory effects mediated via suppression of
arachidonic acid lipoxygenase (LOX) pathway and elevation of
nitric oxide (NO); and amelioration of dyslipidaemia mediated via
fatty acid oxidation. The regulatory patterns of QSYQ on key genes were confirmed by western blot, immunohistochemistry analysis and measurement of plasma
lipids, which further validated the
therapeutic effects of QSYQ proposed in this study. Conclusions: QSYQ exerts multipronged
therapeutic effects on AMI, by concurrently alleviating VR progression, attenuating
inflammation induced by
arachidonic acid LOX pathway and NO production; and ameliorating dyslipidaemia.