Thrombolytic therapy or percutaneous coronary intervention for myocardial infarction often cause myocardial ischemia/reperfusion injury (MIRI) and poor prognosis of patients. This study aimed to explore the protective effect and potential mechanism of hydromorphone hydrochloride (HH) on MIRI. Fifty Sprague–Dawley male rats were randomly divided into Sham group, I/R group, HH-pre group, HH-post group, and HH-pre + post group. Except Sham group, MIRI models were established by ligating and relaxing the left anterior descending coronary artery, followed by tail vein injection of HH (0.3 μmol/L) 10 min before ligation (HH-pre group), 10 min after reperfusion (HH-post group), and twice at the above two time points (HH-pre + post group). After intervention, the cardiac function of rats was evaluated by echocardiography, and the levels of myocardial injury markers, oxidative stress indicators, and mitochondrial function indicators were detected. Next, the myocardial infarction area was evaluated by 2,3,5-triphenyltetrazolium chloride staining, mitochondrial biogenesis, and phosphoinositide 3 kinase (PI3K)/protein kinase B (Akt) signaling pathway by western blot. Compared with the I/R group, HH intervention improved cardiac function, decreased myocardial infarction area, reduced serum myocardial injury markers, alleviated oxidative stress, improved mitochondrial function, up-regulated mitochondrial biogenesis, and activated PI3K/Akt signaling pathway. Moreover, the HH-pre + post group was superior to the HH-pre and HH-post groups in the above aspects. Collectively, HH had protective effect on MIRI rats, and HH preconditioning combined with postconditioning showed optimal efficacy. Such efficacy may be achieved by promoting mitochondrial biogenesis to improve mitochondrial function and reduce oxidative stress, and activating the PI3K/Akt signaling pathway.

中文翻译：

---

盐酸氢吗啡酮预处理联合后处理通过改善线粒体功能、激活PI3K/Akt信号通路减轻大鼠心肌缺血/再灌注损伤

心肌梗死的溶栓治疗或经皮冠状动脉介入治疗常引起心肌缺血/再灌注损伤（MIRI），患者预后不良。本研究旨在探讨盐酸氢吗啡酮（HH）对 MIRI 的保护作用及其潜在机制。 50只Sprague-Dawley雄性大鼠随机分为Sham组、I/R组、HH-pre组、HH-post组和HH-pre + post组。除Sham组外,MIRI模型均采用结扎、舒张左冠状动脉前降支,结扎前10 min(HH-pre组)、再灌注后10 min(HH-pre组)尾静脉注射HH(0.3 μmol/L)建立MIRI模型。后组），并在上述两个时间点两次（HH-前+后组）。干预后,采用超声心动图评估大鼠心功能,检测心肌损伤标志物、氧化应激指标、线粒体功能指标的水平。接下来，通过2,3,5-三苯基氯化四唑染色、线粒体生物合成和蛋白质印迹法的磷酸肌醇3激酶（PI3K）/蛋白激酶B（Akt）信号通路评估心肌梗死面积。与I/R组相比，HH干预改善了心功能，减少了心肌梗死面积，减少了血清心肌损伤标志物，减轻了氧化应激，改善了线粒体功能，上调了线粒体生物合成，激活了PI3K/Akt信号通路。而且HH-pre+post组在上述方面均优于HH-pre和HH-post组。总体而言，HH对MIRI大鼠具有保护作用，且HH预处理联合后处理显示出最佳疗效。这种功效可以通过促进线粒体生物发生以改善线粒体功能并减少氧化应激以及激活 PI3K/Akt 信号通路来实现。