Pravastatin 對於已用CS-866治療之心肌梗塞大鼠其心室再塑型之影響探討(2/2)

Abstract

心肌梗塞後之間隙孔重組係產生心律 不整之原因。先前研究顯示statins 可減少 心律不整，其機轉未明。本研究在探討 statins 可藉由增強梗塞邊緣處之連接素43 之表現而降低心律不整。在綁完左前降冠 狀動脈之雄大鼠任意分配到vehicle ， pravastatin，mevalonate 和混和pravastatin + mevalonate 四週，與對照組做比較，發現 pravastatin 可增強梗塞邊緣之連接素43 之 表現。共軛焦顯微鏡證實此種變化。而心 律不整之分數對照組比pravastatin 者高。 但若加入mevalonate 後，這些效果則消失。 結論：心肌梗塞後，若給予pravastatin 可藉由增強連接素43 之表現而降低心律不 整之程度。

Gap junction remodeling after infarction appears to be an important feature of anatomical substrates of ventricular arrhythmias. Statins have been shown to reduce post-operation arrhythmias. However, the involved mechanisms remain unclear. The present study was to determine whether the antiarrhythmic effect of statins is associated with an increased expression of connexin43 at the border of infarction. To elucidate the effects, we conducted experimental infarction in rats and connexin43 remodeling was investigated by immunoconfocal and Western blot analysis. After ligation of the anterior descending artery, male normocholesterolemic rats were randomized to either vehicle, pravastatin treatment, mevalonate, or combination of pravastatin and mevalonate for 4 weeks. In contrast to myocytes from the border zone in the vehicle group, which showed the amount of Cx43 proteins decreased as assessed by Western blot, pravastatin-treated rats showed significantly increased Cx43 immunostaining. Confocal microscopy confirmed the changes of the junctional complex. Arrhythmic scores during programmed stimulation were significantly higher in the vehicle than those treated with pravastatin. These beneficial effects of pravastatin were reversed by the addition of mevalonate, implicating HMG-CoA reductase as the relevant target of these drugs.