Tetramethylpyrazine induces heme oxygenase-1 expression and attenuates myocardial ischemia/reperfusion injury in rats.
The accumulation of oxygen free radicals and activation of neutrophils are strongly implicated as pathophysiological mechanisms mediating myocardial ischemia/reperfusion injury. Heme oxygenase-1 (HO-1) has been reported to play a protective role in oxidative tissue injuries. In this study, the cardioprotective activity of tetramethylpyrazine (TMP), an active ingredient of Chinese medicinal herb Ligusticum wallichii Franchat, was evaluated in an open-chest anesthetized rat model of myocardial ischemia/reperfusion injury. Pretreatment with TMP (5 and 10 mg/kg, i.v.) before left coronary artery occlusion significantly suppressed the occurrence of ventricular fibrillation. After 45 min of ischemia and 1 h of reperfusion, TMP (5 and 10 mg/kg) caused a significant reduction in infarct size and induced HO-1 expression in ischemic myocardium. The HO inhibitor ZnPP (50 microg/rat) markedly reversed the anti-infarct action of TMP. Superoxide anion production in ischemic myocardium after 10 min reperfusion was inhibited by TMP. Furthermore, TMP (200 and 500 microM) significantly suppressed fMLP (800 nM)-activated human neutrophil migration and respiratory burst. In conclusion, TMP suppresses ischemia-induced ventricular arrhythmias and reduces the infarct size resulting from ischemia/reperfusion injury in vivo. This cardioprotective activity of TMP may be associated with its antioxidant activity via induction of HO-1 and with its capacity for neutrophil inhibition.
Chen
Shu-Ying
SY
Department of Nursing, HungKuang University, Taichung, Taiwan.
Hsiao
George
G
Hwang
Hwong-Ru
HR
Cheng
Pao-Yun
PY
Lee
Yen-Mei
YM
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000517:prevention & control; D002633:Chemotaxis / Q000187:drug effects; D005343:Fibrinolytic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015870:Gene Expression; D051547:Heme Oxygenase-1 / Q000187:drug effects*; D006801:Humans; D030004:Ligusticum; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology; D017202:Myocardial Ischemia / Q000188:drug therapy; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy*; D009206:Myocardium / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects; D010936:Plant Extracts / Q000627:therapeutic use; D011719:Pyrazines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D016897:Respiratory Burst / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism
D005343:Fibrinolytic Agents; D010936:Plant Extracts; D011719:Pyrazines; D013481:Superoxides; D051547:Heme Oxygenase-1; C017953:tetramethylpyrazine