Tetramethylpyrazine and Astragaloside IV Synergistically Ameliorate Left Ventricular Remodeling and Preserve Cardiac Function in a Rat Myocardial Infarction Model

Tetramethylpyrazine (TMP) and astragaloside IV (AGS-IV) are herbal ingredients that have been demonstrated in animal models to limit infarct size and protect cardiomyocytes in the acute phase of myocardial infarction (MI), yet their long-term cardioprotective effects have not been evaluated. In this study, TMP and/or AGS-IV were administrated to rats for 14 days after MI. Echocardiography revealed that the left ventricular (LV) dimensions and cardiac function were preserved in the MI rats with TMP and AGS-IV treatment, compared with untreated MI rats. Moreover, the LV dimensions and cardiac function in the MI rats with TMP and AGS-IV cotreatment were comparable with the sham-operated rats. In addition, TMP and AGS-IV synergistically inhibited LV fibrosis by attenuating MI-induced collagen deposition and elevation of transforming growth factor β1. TMP and AGS-IV, alone or in synergy, enhanced angiogenesis in the infarcted myocardium and reduced cardiac hypertrophy of the remote myocardium after MI. Furthermore, TMP and AGS-IV mutually upregulated the expression of Sonic hedgehog (Shh), Smoothened, and Glioblastoma-2, the receptor and signal transducer of Shh signaling pathway, in the infarcted myocardium. In summary, in the circumstance of the irreversible ischemic injury, the antifibrotic, and pro-angiogenic properties of TMP and AGS-IV on the nonaffected tissues contribute to the cardioprotection in the healing phase post MI, and the cardioprotective effects are likely to be mediated through the Shh pathway.