Diabetes exacerbates myocardial ischemia/reperfusion (IR) injury by incompletely understood mechanisms. We explored whether diabetes diminished BAG3/Bcl-2/Nrf-2/HO-1-mediated cardioprotection and overproduced oxidative stress contributing to exaggerated IR injury. Streptozotocin-induced diabetes enhanced hyperglycemia, cardiac NADPH oxidase p22/p67 expression, malondialdehyde amount and leukocyte infiltration, altered the mesenteric expression of 4-HNE, CaSR, p-eNOS and BAG3 and impaired microvascular reactivity to the vasoconstrictor/vasodilator by a wire myography. In response to myocardial IR, diabetes further depressed BAG3/Bcl-2/Nrf-2/HO-1 expression, increased cleaved-caspase 3/poly(ADP-ribose) polymerase (PARP)/TUNEL-mediated apoptosis and exacerbated IR-induced left ventricular dysfunction characterized by further depressed microcirculation, heart rate, left ventricular systolic pressure and peak rate of pressure increase/decrease (±dp/dt) and elevated left ventricular end-diastolic pressure (LVEDP) and Evans blue-2,3,5-triphenyltetrazolium chloride-stained infarct size in diabetic hearts. Our results implicated diabetes exacerbated IR-induced myocardial dysfunction through downregulated BAG3/Bcl-2/Nrf-2/HO-1 expression, increased p22/p67/caspase 3/PARP/apoptosis-mediated oxidative injury and impaired microvascular reactivity.

中文翻译：

---

糖尿病会上调氧化应激并下调心脏保护作用，从而加剧大鼠的心肌缺血/再灌注损伤。

糖尿病通过不完全了解的机制加剧了心肌缺血/再灌注（IR）损伤。我们探讨了糖尿病是否减少了BAG3 / Bcl-2 / Nrf-2 / HO-1介导的心脏保护作用，并过度产生了氧化应激，从而导致IR损伤加剧。链脲佐菌素诱发的糖尿病会增强高血糖，心脏NADPH氧化酶p22 / p67表达，丙二醛含量和白细胞浸润，改变4-HNE，CaSR，p-eNOS和BAG3的肠系膜表达，并通过线肌造影术削弱对血管收缩剂/血管扩张剂的微血管反应性。响应心肌IR，糖尿病使BAG3 / Bcl-2 / Nrf-2 / HO-1表达进一步降低，裂解半胱天冬酶3 /聚（ADP-核糖）聚合酶（PARP）/ TUNEL介导的细胞凋亡增加，并加剧IR诱导的左心功能不全，其特征是微循环进一步降低，心率，左心室收缩压和压力增/减的峰值速率（±dp / dt）和升高的左心室舒张末期血压（LVEDP）和伊万氏蓝2,3,5-三苯基四唑氯化物在糖尿病心脏中的梗塞面积变大。我们的结果暗示糖尿病通过下调BAG3 / Bcl-2 / Nrf-2 / HO-1表达，增加p22 / p67 / caspase 3 / PARP /凋亡介导的氧化损伤和微血管反应性受损而加剧IR引起的心肌功能障碍。糖尿病心脏左室收缩压和峰值压力增/减率（±dp / dt）和左室舒张末期终压（LVEDP）升高和Evans blue-2,3,5-三苯四唑氯化物在糖尿病心脏中的梗塞面积呈染色性。我们的结果暗示糖尿病通过下调BAG3 / Bcl-2 / Nrf-2 / HO-1表达，增加p22 / p67 / caspase 3 / PARP /凋亡介导的氧化损伤和微血管反应性受损而加剧IR引起的心肌功能障碍。糖尿病心脏左室收缩压和峰值压力增/减率（±dp / dt）和左室舒张末期终压（LVEDP）升高和Evans blue-2,3,5-三苯四唑氯化物在糖尿病心脏中的梗塞面积呈染色性。我们的结果暗示糖尿病通过下调BAG3 / Bcl-2 / Nrf-2 / HO-1表达，增加p22 / p67 / caspase 3 / PARP /凋亡介导的氧化损伤和微血管反应性受损而加剧IR引起的心肌功能障碍。