Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical College, China.
Biol Pharm Bull. 2010;33(3):444-9. doi: 10.1248/bpb.33.444.
Diabetes impairs the expression and function of endogenous growth factors, leading to increased cardiovascular events in diabetic patients. Supplementation of fibroblast growth factors (FGFs) protected the heart from ischemia/reperfusion (I/R)-induced injury in animal models. However, it has not yet been tested in diabetic heart. The present study was thus to clarify whether basic fibroblast growth factor (bFGF) could protect the heart from I/R-induced damage under diabetic conditions using a rat model. Male Sprague Dawley rats were used to induce diabetes by intraperitoneal injection of streptozotocin. Eight weeks later, I/R injury was generated in diabetic rats and age-matched non-diabetic rats. All I/R rats were administrated bFGF or saline through intramyocardial injection. Seven days after I/R, cardiac infarction, structural changes, cell death and blood vessel density, serum malondialdehyde (MDA) and cardiac enzyme lactate dehydrogenase (LDH) were examined. We found that I/R induced significant increases in the cardiac infarction, blood MDA contents and LDH activities, and the expression of caspase-3. Treatment of I/R rats with bFGF simultaneously with reperfusion significantly attenuated I/R-induced pathological changes, along with a significant increase in the cardiac blood vessel density in both diabetic and non-diabetic rates. The protective effects of bFGF on I/R-induced cardiac injury in diabetic group are less than those in non-diabetic group. The results indicated that bFGF provide a protection of the heart against I/R-induced oxidative damage, cell death and infarction under diabetic conditions.
糖尿病会损害内源性生长因子的表达和功能,导致糖尿病患者心血管事件增加。成纤维细胞生长因子(FGFs)的补充可以保护心脏免受动物模型中缺血/再灌注(I/R)引起的损伤。然而,它尚未在糖尿病心脏中进行测试。因此,本研究旨在使用大鼠模型阐明碱性成纤维细胞生长因子(bFGF)是否可以在糖尿病条件下保护心脏免受 I/R 引起的损伤。雄性 Sprague Dawley 大鼠通过腹腔注射链脲佐菌素诱导糖尿病。8 周后,在糖尿病大鼠和年龄匹配的非糖尿病大鼠中产生 I/R 损伤。所有 I/R 大鼠均通过心肌内注射给予 bFGF 或生理盐水。I/R 后 7 天,检查心脏梗死、结构变化、细胞死亡和血管密度、血清丙二醛(MDA)和心脏酶乳酸脱氢酶(LDH)。我们发现,I/R 导致心脏梗死、血液 MDA 含量和 LDH 活性以及 caspase-3 表达显著增加。在再灌注时同时用 bFGF 治疗 I/R 大鼠显著减轻了 I/R 引起的病理变化,同时糖尿病和非糖尿病大鼠的心脏血管密度均显著增加。bFGF 对糖尿病组 I/R 引起的心脏损伤的保护作用小于非糖尿病组。结果表明,bFGF 在糖尿病条件下为心脏提供了对 I/R 引起的氧化损伤、细胞死亡和梗死的保护。