Cardiovascular Surgery, Methodist Hospital, Indiana University School of Medicine, Indianapolis, IN, USA.
Surgery. 2011 Aug;150(2):278-83. doi: 10.1016/j.surg.2011.06.006.
Stem cells protect the heart from ischemic damage in part by the release of cytoprotective growth factors, particularly vascular endothelial growth factor (VEGF). Production of VEGF is regulated in part by levels of the transcription factor hypoxia inducible factor 1-α (HIF-1α). Dimethyloxalylglycine (DMOG) prevents the deactivation of HIF-1α and increases VEGF production. However, the effects of systemic DMOG treatment on myocardial tolerance for ischemia are unknown. We hypothesized that systemic pretreatment with DMOG would improve myocardial ischemic tolerance.
To study this hypothesis, adult male rats were randomly given an intraperitoneal injection of DMOG (40 mg/kg in 1 mL saline, n = 5) or saline (1 mL, n = 6) 24 h before cardiectomy and isolated heart perfusion. All hearts were subjected to 15 min equilibration, 25 min ischemia and 40 min reperfusion. Myocardial function was continuously monitored. Following reperfusion, myocardial homogenates were analyzed for HIF-1α and VEGF production.
We observed that hearts in the DMOG group exhibited greater recovery of left ventricular developed pressure LVDP, +dP/dt and -dP/dt. Myocardial HIF-1α and VEGF levels were increased by DMOG therapy.
In conclusion, systemic pretreatment with DMOG augments post-ischemic myocardial functional recovery through increased HIF-1α levels and greater VEGF production.
干细胞通过释放细胞保护生长因子，特别是血管内皮生长因子（VEGF），部分保护心脏免受缺血性损伤。VEGF 的产生部分受转录因子缺氧诱导因子 1-α（HIF-1α）的水平调节。二甲基草酰甘氨酸（DMOG）可防止 HIF-1α失活并增加 VEGF 的产生。然而，全身给予 DMOG 对心肌缺血耐受性的影响尚不清楚。我们假设全身给予 DMOG 预处理可提高心肌缺血耐受性。
为了研究这一假设，成年雄性大鼠在心脏切除术和离体心脏灌注前 24 小时随机接受腹腔注射 DMOG（40 mg/kg，生理盐水 1 mL，n = 5）或生理盐水（1 mL，n = 6）。所有心脏均进行 15 分钟平衡，25 分钟缺血和 40 分钟再灌注。连续监测心肌功能。再灌注后，分析心肌匀浆中的 HIF-1α 和 VEGF 产生。
我们观察到 DMOG 组的心脏表现出左心室发展压 LVDP、+dP/dt 和-dP/dt 的更大恢复。DMOG 治疗增加了心肌 HIF-1α 和 VEGF 水平。
总之，全身给予 DMOG 通过增加 HIF-1α 水平和增加 VEGF 产生来增强缺血后心肌功能的恢复。
