Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Henan, PR China; Department of Cardiology, The First Affiliated Hospital of Henan University of Chinese Medicine, Henan, PR China.
Department of Critical Care Medicine, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, PR China.
Biochem Biophys Res Commun. 2019 Oct 20;518(3):554-559. doi: 10.1016/j.bbrc.2019.08.080. Epub 2019 Aug 22.
Hyperglycemia-induced endothelial dysfunction is generally believed to be the basis of diabetic vascular complications. Dopamine receptors is known to play an important protective role in diabetes. However, the protective effect of dopamine receptors against hyperglycemia-induced endothelial damage in diabetic rats is still unknown. In the present study, we established a cell model of hyperglycemia-induced endothelial dysfunction by treating human umbilical vein endothelial cells (HUVEC) with high glucose. MTT and lactate dehydrogenase assays results showed that high glucose treatment significantly reduced the cell viability and down-regulated dopamine D receptor. Pre-treatment with PD168077, a specific D receptor agonist, greatly improved endothelial cell viability and decreased apoptosis. Furthermore, pharmacological inhibition of phosphoinositide 3-kinase (PI3K) and endothelial nitric oxide synthase (eNOS) eliminated the protective effect of D receptor against endothelial injury. More importantly, the expression level of D receptor was also dramatically down-regulated in the arterial endothelium of rats with streptozotocin-(STZ)-induced diabetes, and the STZ-induced impairment of acetylcholine-induced vasodilation was reversed by activation of D receptor. In conclusion, our results indicated that dopamine D receptor protected against hyperglycemia-induced endothelial dysfunction via the PI3K/eNOS pathway, which may provide a novel strategy in the treatment of diabetes.
高血糖诱导的内皮功能障碍被普遍认为是糖尿病血管并发症的基础。多巴胺受体在糖尿病中发挥着重要的保护作用。然而，多巴胺受体对糖尿病大鼠高血糖诱导的内皮损伤的保护作用尚不清楚。在本研究中，我们通过用高葡萄糖处理人脐静脉内皮细胞（HUVEC）建立了高血糖诱导的内皮功能障碍的细胞模型。MTT 和乳酸脱氢酶检测结果表明，高葡萄糖处理显著降低了细胞活力并下调了多巴胺 D 受体。多巴胺 D 受体的特异性激动剂 PD168077 的预处理极大地提高了内皮细胞活力并减少了细胞凋亡。此外，磷酸肌醇 3-激酶（PI3K）和内皮型一氧化氮合酶（eNOS）的药理学抑制消除了 D 受体对内皮损伤的保护作用。更重要的是，链脲佐菌素（STZ）诱导的糖尿病大鼠动脉内皮中多巴胺 D 受体的表达水平也显著下调，而 D 受体的激活逆转了 STZ 诱导的乙酰胆碱诱导的血管舒张受损。总之，我们的结果表明，多巴胺 D 受体通过 PI3K/eNOS 通路保护高血糖诱导的内皮功能障碍，这可能为糖尿病的治疗提供一种新策略。
