Bakuchiol attenuates myocardial ischemia reperfusion injury by maintaining mitochondrial function: the role of silent information regulator 1
Bakuchiol attenuates myocardial ischemia reperfusion injury by maintaining mitochondrial function: the role of silent information regulator 1
复制标题
补骨脂酚通过维持线粒体功能减轻心肌缺血再灌注损伤：沉默信息调节因子1的作用
DOI：
10.1007/s10495-016-1225-6
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发表时间：
2016-05-01
期刊：
影响因子：
7.2
通讯作者：
Jin, Zhenxiao
中科院分区：
文献类型：
--
作者：
Feng, Jianyu;Yang, Yang;Jin, Zhenxiao
缺血再灌注（IR）损伤（IRI）与心脏手术和缺血性心脏病的不良预后相关，并导致线粒体氧化应激和细胞死亡。沉默信息调节因子 1 (SIRT1) 是组蛋白脱乙酰酶家族的成员，具有抗 IRI 作用。补骨脂酚 (BAK) 是白藜芦醇的类似物和从补骨脂（豆科）种子中分离出来的单萜酚，可保护组织免受损伤。本研究旨在研究 BAK 治疗对心肌 IRI 的保护作用，并阐明这些作用的潜在机制。在诱导 IR 之前，将分离的大鼠心脏或心肌细胞在不存在或存在 SIRT1 抑制剂 Sirtinol 和 SIRT1 siRNA 的情况下暴露于 BAK。 BAK 具有心脏保护作用，缺血后心脏功能得到改善，心肌细胞凋亡减弱，多种生化参数发生变化（包括抗凋亡蛋白 Bcl2 水平升高、促凋亡蛋白 Bax 水平降低以及裂解的 Caspase 3 水平降低）。然而，Sirtinol 和 SIRT1 siRNA 均通过抑制 SIRT1 信号传导来阻断 BAK 诱导的心脏保护作用。此外，BAK还显着增加线粒体琥珀酸脱氢酶、细胞色素c氧化酶和线粒体超氧化物歧化酶的活性，并减少丙二醛的产生。这些发现表明 BAK 显着减轻了 IR 诱导的线粒体氧化损伤。然而，Sirtinol 和 SIRT1 siRNA 消除了 BAK 依赖性线粒体功能。总之，我们的结果表明，BAK 治疗通过激活 SIRT1/PGC-1α 信号传导来减轻 IR 诱导的线粒体氧化损伤，从而减轻 IRI。
Ischemia reperfusion (IR) injury (IRI) is associated with poor prognoses in the settings of both cardiac surgery and ischemic heart disease and causes mitochondrial oxidative stress and cell death. Silent information regulator 1 (SIRT1), a member of the histone deacetylase family, exerts anti-IRI effects. Bakuchiol (BAK), an analog of resveratrol and a monoterpene phenol isolated from the seeds ofPsoralea corylifolia(Leguminosae), protects tissues from injury. This study was designed to investigate the protective effects of BAK treatment in the setting of myocardial IRI and to elucidate the potential mechanism of those effects. Prior to induction of IR, isolated rat hearts or cardiomyocytes were exposed to BAK in either the absence or presence of the SIRT1 inhibitors Sirtinol and SIRT1 siRNA. BAK exerted cardioprotective effects, as evidenced by the improvements noted in cardiac function following ischemia, attenuated myocardial apoptosis, and changes in several biochemical parameters (including increases in the level of the anti-apoptotic protein Bcl2, decreases in the level of the pro-apoptotic protein Bax, and decreases in the cleaved Caspase 3 level). However, Sirtinol and SIRT1 siRNA each blocked BAK-induced cardioprotection by inhibiting SIRT1 signaling. Additionally, BAK significantly increased the activities of mitochondrial succinate dehydrogenase, cytochrome c oxidase, and mitochondrial superoxide dismutase and decreased the production of malondialdehyde. These findings suggested that BAK significantly attenuated IR-induced mitochondrial oxidative damage. However, Sirtinol and SIRT1 siRNA abolished BAK-dependent mitochondrial function. In summary, our results demonstrate that BAK treatment attenuates IRI by attenuating IR-induced mitochondrial oxidative damage via the activation of SIRT1/PGC-1α signaling.