Department of Pharmacology, Poznan University of Medical Sciences, Rokietnicka 5d, 60-805 Poznań, Poland.
Department of Pharmacology, West Kazakhstan Marat Ospanov State Medical University, Mareshev str. 68, Aktobe 030019, Kazakhstan.
Eur J Pharm Sci. 2018 May 30;117:41-47. doi: 10.1016/j.ejps.2018.02.009. Epub 2018 Feb 7.
Alpha-lipoic acid (ALA), widely known as an antioxidant, modifies also serum levels of angiogenic factors in type 2 diabetic patients. These pharmacological activities may influence the status of the cardiovascular system. Taking into consideration that diabetes is related to the increased cardiovascular risk we investigated several effects of ALA on angiogenic factors in the myocardium and in the aortal wall using a rat model of type 2 diabetes.
Diabetes was induced in Wistar rats by a fat-rich diet and by intraperitoneal injection of a small dose of streptozotocin (30 mg/kg). Animals were divided into 3 groups: ALA-treated type 2 diabetes rat model, placebo-treated type 2 diabetes rat model and placebo-treated non-diabetic rats. ALA was administered orally once a day, 20 mg/kg, for 8 consecutive weeks. mRNA VEGF, VEGF-R1 and VEGF-R2 expression was measured in the myocardium and the aortal wall, simultaneously with circulating VEGF and circulating endothelial cells (cEC) and endothelial progenitor cells (cEPC).
ALA induced pro-angiogenic effect in the myocardium of rats with diabetes increasing mRNA VEGF expression and decreasing mRNA VEGFR-1 expression, while in the aortal wall ALA increased mRNA VEGFR-2 and VEGFR-1 expression. cVEGF in the ALA-treated group was higher comparing to both control groups. It was revealed that cEC percentage in the ALA-treated group was decreased with no effect on the percentage of cEPC.
In summary, the current data provide novel findings about potential beneficial effects of ALA on angiogenic factors in the cardiovascular system, especially on myocardium, in the course of type 2 diabetes.
α-硫辛酸（ALA）作为一种抗氧化剂广为人知，它还可以调节 2 型糖尿病患者的血管生成因子水平。这些药理作用可能会影响心血管系统的状态。考虑到糖尿病与心血管风险增加有关，我们使用 2 型糖尿病大鼠模型研究了 ALA 对心肌和主动脉壁中血管生成因子的几种作用。
通过高脂肪饮食和小剂量链脲佐菌素（30mg/kg）腹腔注射诱导 Wistar 大鼠发生糖尿病。动物分为 3 组：ALA 治疗 2 型糖尿病大鼠模型、安慰剂治疗 2 型糖尿病大鼠模型和安慰剂治疗非糖尿病大鼠。ALA 每天口服一次，20mg/kg，连续 8 周。同时测量心肌和主动脉壁中 VEGF、VEGF-R1 和 VEGF-R2 的 mRNA 表达，以及循环 VEGF 和循环内皮细胞（cEC）和内皮祖细胞（cEPC）。
ALA 诱导糖尿病大鼠心肌产生促血管生成作用，增加 mRNA VEGF 表达，降低 mRNA VEGFR-1 表达，而在主动脉壁中，ALA 增加 mRNA VEGFR-2 和 VEGFR-1 表达。ALA 治疗组的 cVEGF 高于两组对照。结果表明，ALA 治疗组 cEC 的百分比降低，但对 cEPC 的百分比没有影响。
总之，目前的数据提供了关于 ALA 在 2 型糖尿病过程中对心血管系统中血管生成因子的潜在有益作用的新发现，特别是对心肌。
