Huang Zhouqing, Ye Bozhi, Dai Zhenyu, Wu Xinlei, Lu Zhongqiu, Shan Peiren, Huang Weijian
Department of Cardiology, The Key Laboratory of Cardiovascular Disease of Wenzhou, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
Department of Emergency, The Key Laboratory of Cardiovascular Disease of Wenzhou, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
Mol Med Rep. 2015 Jun;11(6):4678-84. doi: 10.3892/mmr.2015.3322. Epub 2015 Feb 9.
Primary percutaneous coronary intervention, or thombolytic therapy, provides effective myocardial blood reconstruction in patients with acute myocardial infarction to reduce acute myocardial ischemic injury. However, reperfusion can itself induce cardiomyocyte death, termed myocardial reperfusion injury (I/R). Hypoxia/reoxygenation (H/R) induces apoptosis and excessive autophagy among cardiomyocytes, leading to cell death. The present study investigated the effect of curcumin, a natural extract from Curcuma longa, on these two cellular processes in H9c2 myocytes. The levels of cellular apoptosis and autophagy were found to be upregulated in the H9c2 myocytes during H/R and were correlated with a reduced rate of cell survival. However, curcumin significantly suppressed the levels of H/R‑induced apoptosis (expression of annexin V) and autophagy (LC3B‑II/LC3B‑I ratio) in the H9c2 myocytes and promoted cell survival. Additionally, the expression of B‑cell lymphoma 2 (Bcl‑2) was significantly downregulated and the expression levels of Bcl‑2‑associated X protein, beclin‑1, Bcl‑2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3) and silent information regulation 1 (SIRT1) were significantly upregulated in myocytes following H/R injury. These effects on the expression of these proteins were reversed by curcumin treatment. These findings suggested that the protective effect of curcumin against H/R injury in the H9c2 myocytes was through the inhibition of apoptosis and autophagy by inducing the expression of Bcl‑2 and inhibiting the expression levels of Bax, beclin‑1, BNIP3 and SIRT1. Therefore, curcumin may offer a promising therapeutic approach for the treatment of cardiomyocyte injury resulting from I/R.
直接经皮冠状动脉介入治疗或溶栓治疗可有效重建急性心肌梗死患者的心肌血流，以减轻急性心肌缺血损伤。然而，再灌注本身可诱导心肌细胞死亡，即心肌再灌注损伤（I/R）。缺氧/复氧（H/R）可诱导心肌细胞发生凋亡和过度自噬，进而导致细胞死亡。本研究调查了姜黄素（一种从姜黄中提取的天然提取物）对H9c2心肌细胞这两种细胞过程的影响。研究发现，H9c2心肌细胞在H/R过程中细胞凋亡和自噬水平上调，且与细胞存活率降低相关。然而，姜黄素可显著抑制H9c2心肌细胞中H/R诱导的凋亡水平（膜联蛋白V的表达）和自噬水平（LC3B-II/LC3B-I比率），并促进细胞存活。此外，H/R损伤后，心肌细胞中B细胞淋巴瘤2（Bcl-2）的表达显著下调，而Bcl-2相关X蛋白、beclin-1、Bcl-2/腺病毒E1B 19 kDa相互作用蛋白3（BNIP3）和沉默信息调节因子1（SIRT1）的表达水平显著上调。姜黄素处理可逆转这些对这些蛋白质表达的影响。这些发现表明，姜黄素对H9c2心肌细胞H/R损伤的保护作用是通过诱导Bcl-2表达并抑制Bax、beclin-1、BNIP3和SIRT1的表达水平来抑制凋亡和自噬实现的。因此，姜黄素可能为治疗I/R所致心肌细胞损伤提供一种有前景的治疗方法。
