大蒜素通过调控SIRT3/PPARγ信号通路促进心衰大鼠血管再生和心功能改善

Allicin promotes angiogenesis and cardiac function improvement in rats with heart failure by regulating the SIRT3/PPARγsignaling pathway

目的探究大蒜素通过调控Sirtuins3(SIRT3)/过氧化物酶体增殖物激活受体γ(PPARγ)信号通路促进心力衰竭(HF)大鼠血管再生和心功能改善的机制。方法HF大鼠模型通过腹主动脉结扎得到。将HF模型大鼠随机分为HF组、HF+低剂量大蒜素组和HF+高剂量大蒜素组(n=15)。同期健康大鼠15只作为对照组。大蒜素的灌胃剂量分别为15 mg/kg·d和30 mg/kg·d。分析大蒜素对HF大鼠心肌损伤、纤维化、凋亡和血管生成的影响。比较各组SIRT3和PPARγmRNA和蛋白的表达量。结果四组大鼠的上述指标比较差异显著(P<0.05)。HF组的射血分数、血管数目、SIRT3和PPARγmRNA水平显著低于对照组(P<0.05);左室舒张末期内径(LVEDD)和左室收缩末期内径(LVESD)、纤维化水平、凋亡指数显著高于对照组(P<0.05)。HF+低剂量大蒜素组的射血分数、血管数目、SIRT3和PPARγmRNA水平显著高于HF组;LVEDD和LVESD、纤维化水平、凋亡指数显著低于HF组(P<0.05)。HF+高剂量大蒜素组的射血分数、血管数目、SIRT3和PPARγmRNA水平显著高于HF组和HF+低剂量大蒜素组;LVEDD和LVESD、纤维化水平、凋亡指数显著低于HF组和HF+低剂量大蒜素组(P<0.05)。结论大蒜素可能通过剂量依赖性的诱SIRT3/PPARγ通路促进血管生成,从而抑制心肌细胞凋亡和纤维化,提高心脏射血功能。

Objective To the mechanism of allicin to promote heart failure(HF)rat angiogenesis and cardiac function through regulating Sirtuins3(SIRT3)/peroxisome proliferator activated receptorγ(peroxisome proliferator activated receptorγ,PPARγ)signaling pathway.Method The HF rat model was obtained by ligating the abdominal aorta.The HF model rats were randomly divided into HF group,HF+low-dose allicin group and HF+high-dose allicin group(n=15).During the same period,15 healthy rats served as the control group.The gavage doses of allicin were 15 mg/kg·d and 30 mg/kg·d,respectively.The effects of allicin on myocardial injury,fibrosis,apoptosis and angiogenesis in HF rats were detected.The expression levels of SIRT3 and PPARγmRNA and protein in each group were compared.Results The above indicators of the four groups of rats were significantly different(P<0.05).The ejection fraction,number of blood vessels,SIRT3 and PPARγmRNA levels in the HF group were significantly lower than those in the control group(P<0.05);LVEDD and LVESD,fibrosis level,apoptosis index were significantly higher than those of the control group(P<0.05).The ejection fraction,number of blood vessels,SIRT3 and PPARγmRNA levels in the HF+low-dose allicin group were significantly higher than those in the HF group;LVEDD and LVESD,fibrosis level and apoptosis index were significantly lower than those in the HF group(P<0.05).The ejection fraction,number of blood vessels,SIRT3 and PPARγmRNA levels in the HF+high-dose allicin group were significantly higher than those of the HF group and HF+low-dose allicin group;LVEDD and LVESD,fibrosis level,and apoptosis index were significantly lower than those in the HF group and the HF+low-dose allicin group(P<0.05).Conclusion Allicin may induce angiogenesis through dose-dependent induction of SIRT3/PPARγpathway,thereby inhibiting cardiomyocyte apoptosis and fibrosis and improving cardiac ejection function.