Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China.
Department of Medicine, The Hospital of 91208 Troops, PLA Navy, Qingdao, Shandong 266102, China.
Chin Med J (Engl). 2017 Dec 5;130(23):2829-2835. doi: 10.4103/0366-6999.219143.
Safflower extract and aceglutamide (SA) has been used clinically for the treatment of cerebrovascular diseases such as cerebral embolism, hemorrhage, and mental deterioration. This study aimed to investigate the effect and mechanism of SA injection in the recovery of peripheral innervations of diabetic mice.
The C57BL/6 male mice were divided into four groups: normal control group (n = 44), diabetic group (n = 44), diabetic + SA group (diabetic mice treated with SA injection, n = 44), and diabetic + SA + vascular endothelial growth factor receptor (VEGFR)1-BL group (diabetic mice treated with SA injection and VEGFR 1 blocking antibody n = 24). The streptozotocin-induced diabetic mice model and injured peripheral nerve mice model were built. The mice with injured peripheral nerves were intraperitonealy administered with SA injection for successive 21 days. The corneal sensitivity, number of corneal nerve fibers, and contents of vascular endothelial growth factor (VEGF)-B and various neurotrophic factors such as nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF) in corneal tissue of four groups were observed.
The diabetic group showed decreased number of corneal nerve fibers, compared with the control group (P = 0.002). And compared with the diabetic group, the diabetic + SA group showed a significant increase in the number of nerve fibers (P = 0.024) and the contents of VEGF-B, NGF, and GDNF in the cornea (all P < 0.05). However, when the diabetic mice were treated with the blocking antibodies specialized for VEGF-B receptor, the neutralization of VEGFR-1 completely abolished the increased expression of NGF and GDNF stimulated by SA injection.
SA injection could reduce the nerve injury caused by diabetic peripheral neuropathy, and its protective effect might be associated with the promotion of the expressions of VEGF-B, NGF, and GDNF.
红花提取物和乙酰谷酰胺（SA）已临床用于治疗脑栓塞、出血和智力下降等脑血管疾病。本研究旨在探讨 SA 注射液对糖尿病小鼠周围神经恢复的作用及机制。
将雄性 C57BL/6 小鼠分为正常对照组（n=44）、糖尿病组（n=44）、糖尿病+SA 组（糖尿病小鼠给予 SA 注射液治疗，n=44）和糖尿病+SA+血管内皮生长因子受体 1-BL 组（糖尿病小鼠给予 SA 注射液和血管内皮生长因子受体 1 阻断抗体治疗，n=24）。构建链脲佐菌素诱导的糖尿病小鼠模型和损伤周围神经小鼠模型。对损伤周围神经的小鼠连续 21 天腹腔内给予 SA 注射液。观察四组小鼠角膜敏感性、角膜神经纤维数量以及角膜组织中血管内皮生长因子（VEGF）-B 和神经生长因子（NGF）、胶质细胞源性神经营养因子（GDNF）等多种神经营养因子的含量。
糖尿病组与对照组相比，角膜神经纤维数量减少（P=0.002）；与糖尿病组相比，糖尿病+SA 组神经纤维数量明显增加（P=0.024），角膜 VEGF-B、NGF 和 GDNF 含量也明显增加（均 P<0.05）。然而，当糖尿病小鼠用专门针对 VEGF-B 受体的阻断抗体进行治疗时，SA 注射刺激的 NGF 和 GDNF 表达的增加被 VEGFR-1 中和完全阻断。
SA 注射液可减轻糖尿病周围神经病变引起的神经损伤，其保护作用可能与促进 VEGF-B、NGF 和 GDNF 的表达有关。
