Allicin attenuates pathological cardiac hypertrophy by inhibiting autophagy via activation of PI3K/Akt/mTOR and MAPK/ERK/mTOR signaling pathways
Allicin attenuates pathological cardiac hypertrophy by inhibiting autophagy via activation of PI3K/Akt/mTOR and MAPK/ERK/mTOR signaling pathways
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DOI：
10.1016/j.phymed.2018.11.025
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发表时间：
2019-05-01
期刊：
影响因子：
7.9
通讯作者：
Sun Hongli
中科院分区：
文献类型：
--
作者：
Ba Lina;Gao Jingquan;Sun Hongli
背景：心脏肥大是心肌对压力或容量超负荷的适应性反应。最近的证据表明大蒜素可以预防心脏肥大。然而，大蒜素是否通过抑制自噬来缓解心肌肥厚尚不清楚。目的：探讨大蒜素对压力超负荷引起的心肌肥厚的影响，并进一步阐明相关机制。研究设计/方法：通过腹主动脉缩窄（AAC）成功建立大鼠心脏肥大，并通过腹主动脉缩窄（AAC）成功模拟心肌细胞肥大。 血管紧张素 II (Ang II) 体外。通过体内机能实验系统监测血流动力学参数。分别采用体内和体外HE和免疫荧光染色观察细胞表面积的变化。 Western blot检测心脏肥大相关蛋白（BNP和β-MHC）、自噬标志蛋白（LC3-II和Beclin-1）、Akt、PI3K和ERK的表达。结果：大蒜素可以改善心功能，缩小心肌细胞体积，降低BNP和β-MHC蛋白表达。进一步的结果表明，在体内和体外实验中，大蒜素都能降低LC3-II和Beclin-1蛋白的表达。 mTOR的药理学抑制剂雷帕霉素可以拮抗大蒜素对Ang II诱导的心脏肥大和自噬的作用。同时，大蒜素可以促进p-Akt、p-PI3K和p-ERK蛋白的表达。结论：这些发现揭示了大蒜素减轻心肌肥厚的新机制，大蒜素可以通过激活PI3K/Akt/mTOR和MAPK/ERK/mTOR信号通路抑制过度自噬。
Background: Cardiac hypertrophy is an adaptive response of the myocardium to pressure or volume overload. Recent evidences indicate that allicin can prevent cardiac hypertrophy. However, it is not clear whether allicin alleviates cardiac hypertrophy by inhibiting autophagy.Purpose: We aimed to investigate the effects of allicin on pressure overload-induced cardiac hypertrophy, and further to clarify the related mechanism.Study design/methods: Cardiac hypertrophy was successfully established by abdominal aortic constriction (AAC) in rats, and cardiomyocytes hypertrophy was simulated by angiotensin II (Ang II) in vitro. Hemodynamic parameters were monitored by organism function experiment system in vivo. The changes of cell surface area were observed using HE and immunofluorescence staining in vivo and in vitro, respectively. The expressions of cardiac hypertrophy relative protein (BNP and beta-MHC), autophagy marker protein (LC3-II and Beclin-1), Akt, PI3K and ERK were detected by western blot.Results: Allicin could improve cardiac function, and reduce cardiomyocytes size, and decrease BNP and beta-MHC protein expressions. Further results showed that allicin could lower LC3-II and Beclin-1 protein expressions both in vivo and in vitro experiments. And pharmacological inhibitor of mTOR, rapamycin could antagonize the effects of allicin on Ang II-induced cardiac hypertrophy and autophagy. Simultaneously, allicin could promote the expressions of p-Akt, p-PI3K and p-ERK protein.Conclusion: These findings reveal a novel mechanism of allicin attenuating cardiac hypertrophy which allicin could inhibit excessive autophagy via activating PI3K/Akt/mTOR and MAPK/ERK/mTOR signaling pathways.