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.
Departments of *Clinical Pharmacy and Traditional Chinese Medicine Pharmacology; and †Pharmacy, School of Pharmaceutical Sciences, Changchun University of Chinese Medicine, Changchun, China; and ‡Department of Pharmacy, The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, China.
Chuying
C
Wang
Yumei
Y
Li
Xinxin
X
Yang
Shengnan
S
Bi
Yajie
Y
Zhang
Dong
D
Han
Dafang
D
Zhang
D000818:Animals; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D011719:Pyrazines / Q000008:administration & dosage*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012503:Saponins / Q000008:administration & dosage*; D014315:Triterpenes / Q000008:administration & dosage*; D014665:Vasodilator Agents / Q000008:administration & dosage; D016277:Ventricular Function, Left / Q000187:drug effects* / Q000502:physiology; D020257:Ventricular Remodeling / Q000187:drug effects* / Q000502:physiology
D004365:Drugs, Chinese Herbal; D011719:Pyrazines; D012503:Saponins; D014315:Triterpenes; D014665:Vasodilator Agents; C052064:astragaloside A; C017953:tetramethylpyrazine