Nakanishi Nobuhiro, Kaikita Koichi, Oimatsu Yu, Ishii Masanobu, Kuyama Naoto, Arima Yuichiro, Araki Satoshi, Nakamura Taishi, Yamamoto Eiichiro, Tsujita Kenichi
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Division of Cardiovascular Medicine and Nephrology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan.
Heart Vessels. 2025 Jun;40(6):545-556. doi: 10.1007/s00380-024-02480-9. Epub 2024 Nov 5.
5-Aminolevulinic acid (5-ALA) is a naturally occurring metabolic precursor of heme, and 5-ALA combined with ferrous iron can induce heme oxygenase-1 (HO-1) in various cells. In this study, we investigated the cardioprotective effect of 5-ALA after myocardial ischemia/reperfusion (I/R) injury using a murine model.
Male C57BL/6 J mice (10-12 weeks of age and weighing 21-26 g) were pretreated with 100 mg/kg of 5-ALA hydrochloride and 157 mg/kg of sodium ferrous citrate (SFC) or vehicle 48 h, 24 h, and 1 h before I/R, and underwent 50 min of left coronary artery occlusion followed by reperfusion. Infarct area (IA) and area at risk (AAR) were determined by Evans blue and triphenyltetrazolium chloride double staining after reocclusion. Pre-administration with 5-ALA/SFC significantly reduced IA/AAR compared with placebo (34.0% vs. 51.7%, respectively; p = 0.001). Real-time PCR assay after reperfusion showed that mRNA expressions of TNF-α, IL-1β, and BNP were significantly lower, and that of HO-1 was significantly higher in the 5-ALA/SFC group than in the vehicle group in ischemic sites. An inhibition experiment revealed that zinc protoporphyrin IX, an inhibitor of HO-1, inhibited the cardioprotective effects of 5-ALA/SFC.
These results suggest that 5-ALA/SFC might play a cardioprotective role in myocardial I/R injury by attenuating the inflammatory reaction by increasing the expression of HO-1.
5-氨基酮戊酸（5-ALA）是血红素天然存在的代谢前体，5-ALA与亚铁离子结合可在多种细胞中诱导血红素加氧酶-1（HO-1）。在本研究中，我们使用小鼠模型研究了5-ALA对心肌缺血/再灌注（I/R）损伤后的心脏保护作用。
雄性C57BL/6 J小鼠（10-12周龄，体重21-26 g）在I/R前48小时、24小时和1小时分别用100 mg/kg盐酸5-ALA和157 mg/kg柠檬酸亚铁钠（SFC）或赋形剂预处理，然后进行50分钟的左冠状动脉闭塞，随后再灌注。再闭塞后通过伊文思蓝和氯化三苯基四氮唑双重染色确定梗死面积（IA）和危险面积（AAR）。与安慰剂相比，预先给予5-ALA/SFC可显著降低IA/AAR（分别为34.0%和51.7%；p = 0.001）。再灌注后的实时PCR分析显示，缺血部位5-ALA/SFC组中TNF-α、IL-1β和BNP的mRNA表达显著降低，而HO-1的mRNA表达显著高于赋形剂组。抑制实验表明，HO-1抑制剂锌原卟啉IX可抑制5-ALA/SFC的心脏保护作用。
这些结果表明，5-ALA/SFC可能通过增加HO-1的表达减轻炎症反应，从而在心肌I/R损伤中发挥心脏保护作用。
