Yuan Chengjun, Wang Huating, Yuan Zuyi
Pharmazie. 2019 Mar 1;74(3):157-162. doi: 10.1691/ph.2019.8858.
The aim of this study was to observe the effects of HIF-1α activation on myocardial I/R in diabetes. Diabetes was induced in an experimental rat model, and regulators of HIF-1α including KC7F2, deferoxamine and ginsenoside Rg1 were administered to observe the changes on diabetic rats. The results demonstrated that HIF-1α activation could effectively reduce myocardial injury following I/R in diabetic hearts ERK but not MMP-2 signalling pathways. This activation promoted myocardial apoptosis, which was accompanied by modulation of Bax/Bcl-2, caspase-3 and caspase-9 expression following deferoxamine administration. Ginsenoside Rg1 application but not Re can activate HIF-1α, resulting in a similar protectively effect on these pathology processes. Our data demonstrated that ginsenoside Rg1 has a potential therapeutic effect by protecting diabetic hearts after myocardial injury following I/R via HIF-1α activation.
本研究旨在观察缺氧诱导因子-1α(HIF-1α)激活对糖尿病心肌缺血/再灌注(I/R)的影响。在实验大鼠模型中诱导糖尿病,并给予包括KC7F2、去铁胺和人参皂苷Rg1在内的HIF-1α调节剂,以观察糖尿病大鼠的变化。结果表明,HIF-1α激活可有效减轻糖尿病心脏I/R后的心肌损伤,通过细胞外信号调节激酶(ERK)而非基质金属蛋白酶-2(MMP-2)信号通路。这种激活促进了心肌细胞凋亡,在给予去铁胺后,伴随着Bax/Bcl-2、半胱天冬酶-3(caspase-3)和半胱天冬酶-9表达的调节。应用人参皂苷Rg1而非人参皂苷Re可激活HIF-1α,对这些病理过程产生类似的保护作用。我们的数据表明,人参皂苷Rg1通过激活HIF-1α对糖尿病心脏I/R后心肌损伤具有潜在的治疗作用。