Gambogic acid suppresses pressure overload cardiac hypertrophy in rats.
Gambogic acid suppresses pressure overload cardiac hypertrophy in rats.
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藤黄酸抑制大鼠压力超负荷心脏肥大。
DOI：
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发表时间：
2013-11
期刊：
影响因子：
--
通讯作者：
刘金保
中科院分区：
文献类型：
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作者：
刘金保
心脏肥大是心脏对各种心血管刺激的常见反应。病理性心脏肥大最终导致心力衰竭。藤黄酸（Gambogic acid，GA）是从藤黄树的藤黄树脂中分离得到的主要活性成分，具有有效的抗肿瘤和抗炎作用，其作用与抑制NF-κB通路有关。我们和其他人最近报道，GA可以显着抑制蛋白酶体的功能，比传统的蛋白酶体抑制剂毒性小得多。越来越多的证据表明，抑制蛋白酶体可通过阻断NF-κB通路，促进压力超负荷性心肌肥厚的消退。在本研究中，我们检查了GA对压力超负荷或异丙肾上腺素输注诱导的心脏肥大和纤维化的影响，以及心肌NF-κB信号传导的变化。我们观察到腹主动脉缩窄（AAC）或异丙肾上腺素（ISO）可显著增加心脏重量/体重比、心肌细胞体积、间质纤维化和胎儿基因（α-SK-actin和BNP mRNA）的再激活，GA处理可有效抑制上述作用。此外，GA处理消除了AAC或ISO诱导的蛋白酶体糜蛋白酶样活性增加，导致AAC或ISO大鼠心肌中IκB蛋白增加，核部分中NF-κB p65亚基水平降低，NF-κB DNA结合活性降低，IL 2水平降低。结论：GA可能通过抑制蛋白酶体和NF-κB通路抑制压力超负荷或异丙肾上腺素诱导的心肌肥厚和纤维化，为临床治疗心肌肥厚提供了新的思路。
Cardiac hypertrophy is a common response of the heart to a variety of cardiovascular stimuli. Pathological cardiac hypertrophy eventually leads to heart failure. Gambogic acid (GA) is a main active ingredient isolated from the gamboge resin of Garcinia hanburyi trees and has potent anti-tumor and anti-inflammatory effects that are associated with inhibition of the NF-κB pathway. We and others recently reported that GA can significantly inhibit the function of the proteasome with much less toxicity than conventional proteasome inhibitors. The increasing lines of evidence indicate that the inhibition of the proteasome can promote the regression of cardiac hypertrophy induced by pressure overload through the blockade of the NF-κB pathway. In the present study, we examined the effect of GA on pressure overload or isoproterenol infusion induced cardiac hypertrophy and fibrosis, and changes in myocardial NF-κB signaling. We observed that the heart weight/body weight ratio, the size of cardiomyocytes, interstitial fibrosis, and the reactivation of fetal genes (α-SK-actin and BNP mRNA) were markedly increased by abdominal aorta constriction (AAC) or isoproterenol infusion (ISO), all of which were effectively inhibited by GA treatment. Furthermore, GA treatment abolished proteasome chymotrypsin-like activity increases induced by AAC or ISO, led to increased myocardial IκB protein, decreased NF-κB p65 subunit levels in the nuclear fraction, decreased NF-κB DNA-binding activity, and reduced IL2 levels in the myocardium of rats subject to AAC or ISO. In conclusion, GA treatment can suppress cardiac hypertrophy and fibrosis induced by pressure overload or isoproterenol possibly through the inhibition of the proteasome and the NF-κB pathway, suggesting that GA treatment may provide a new strategy to treat cardiac hypertrophy.
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影响因子：
20.1
作者：
Tian Z;Zheng H;Li J;Li Y;Su H;Wang X
通讯作者：
Wang X
DOI：
10.1152/ajpheart.00196.2007
发表时间：
2008-02-01
影响因子：
4.8
作者：
Stansfield, William E.;Tang, Ru-Hang;Selzman, Craig H.
通讯作者：
Selzman, Craig H.
影响因子：
3.4
作者：
Felth, Jenny;Lesiak-Mieczkowska, Karolina;Rickardson, Linda
通讯作者：
Rickardson, Linda
影响因子：
168.9
作者：
Shah, Ajay M.;Mann, Douglas L.
通讯作者：
Mann, Douglas L.
影响因子：
20.1
作者：
Wang X;Pattison JS;Su H
通讯作者：
Su H