Resveratrol Ameliorates Pressure Overload-induced Cardiac Dysfunction and Attenuates Autophagy in Rats
Resveratrol Ameliorates Pressure Overload-induced Cardiac Dysfunction and Attenuates Autophagy in Rats
复制标题
白藜芦醇可改善压力过载引起的大鼠心脏功能障碍并减弱自噬
DOI：
10.1097/fjc.0000000000000290
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发表时间：
2015-10-01
影响因子：
3
通讯作者：
Xian, Shaoxiang
中科院分区：
文献类型：
--
作者：
Wang, Lingjun;Gao, Mengxi;Xian, Shaoxiang
压力超负荷在心力衰竭中具有重要作用，诱导被认为是致病性的心肌细胞中的过度自噬。白藜芦醇有改善压力超负荷引起的心功能不全的作用，但白藜芦醇是否通过调节自噬来改善心功能不全尚不清楚。在这项研究中，通过收缩腹主动脉来诱导大鼠心力衰竭。手术后4周，心力衰竭大鼠被随机分为两组，一组接受白藜芦醇治疗28天（腹腔注射8 mg，中心点kg 21，中心点d（-1）），另一组仅腹腔注射溶媒（丙二醇）。进行超声心动图以评估心脏功能。实时定量聚合酶链反应检测左心室脑利钠肽信使RNA的表达，免疫印迹和免疫组化检测自噬相关蛋白（beclin-1和lamp-1）的表达。透射电镜观察心肌自噬空泡形成，生物发光法测定心肌ATP含量。白藜芦醇治疗可显著改善心力衰竭大鼠的心功能不全，并降低脑钠肽的表达。白藜芦醇下调beclin-1和lamp-1的表达，并抑制衰竭心脏中自噬空泡的形成。此外，白藜芦醇恢复心肌ATP水平和减少磷酸化的AMP激活的蛋白激酶在Thr 172。这些结果表明，白藜芦醇可能通过失活AMP激活的蛋白激酶和恢复ATP抑制压力超负荷性心力衰竭的自噬。因此，白藜芦醇可能对高血压心脏病患者有益。
Pressure overload has an important role in heart failure, inducing excessive autophagy in cardiac myocytes that is considered to be pathogenic. Resveratrol has been reported to improve cardiac dysfunction induced by pressure overload, but it has been unclear whether resveratrol ameliorates cardiac dysfunction by regulating autophagy. In this study, heart failure was induced in rats by constriction of the abdominal aorta. Four weeks after surgery, the rats with heart failure were randomized to treatment with resveratrol ( 8 mg center dot kg21 center dot d(-1) by intraperitoneal injection) for 28 days or to intraperitoneal injection of the vehicle ( propylene glycol) alone. Echocardiography was performed to assess cardiac function. Expression of brain natriuretic peptide messenger RNA in the left ventricle was detected by real-time polymerase chain reaction, whereas expression of proteins associated with autophagy ( beclin-1 and lamp-1) was detected by western blotting and immunohistochemistry. Furthermore, autophagic vacuoles were detected in the heart by transmission electron microscopy, and the myocardial ATP content was measured by the bioluminescence method. Treatment with resveratrol significantly improved cardiac dysfunction and reduced brain natriuretic peptide expression in rats with heart failure. Resveratrol down-regulated beclin-1 and lamp-1 expression and also inhibited the formation of autophagic vacuoles in failing hearts. Furthermore, resveratrol restored the myocardial ATP level and reduced phosphorylation of AMP-activated protein kinase at Thr172. These results suggest that resveratrol may inhibit autophagy through inactivation of AMP-activated protein kinase and restoration of ATP in heart failure induced by pressure overload. Accordingly, resveratrol may be beneficial for patients with hypertensive heart disease.