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目的:探讨桂皮醛对衰老大鼠模型血管内皮功能的影响及相关机制。方法:通过建立24月龄自然衰老的Sprague Dawley(SD)大鼠模型及第14代的衰老人脐静脉内皮细胞模型(HUVECs),以桂皮醛(10μM)进行体外干预,分别以DHE染色和DAF-2DA染色观察桂皮醛对颈动脉内膜和HUVEC中超氧阴离子、一氧化氮水平的影响。以微血管张力测定仪观察桂皮醛对乙酰胆碱诱导的颈动脉内皮依赖性舒张功能和硝酸甘油诱导的非内皮依赖性舒张功能的影响。Western blotting观察磷酸化eNOS水平及Nrf2表达。结果:桂皮醛孵育显著减少改善衰老大鼠颈动脉内膜和衰老HUVEC的ROS水平,促进HUVEC中eNOS的磷酸化,增加NO水平,改善乙酰胆碱诱导的血管内皮依赖性舒张功能,对硝酸甘油诱导的非内皮依赖性舒张功能无显著的影响;Nrf2的抑制剂鸦胆子苦醇可显著阻断桂皮醛的作用。结论:桂皮醛通过Nrf2通路减少衰老相关的ROS生成,增加NO水平从而改善衰老大鼠血管内皮依赖性舒张功能。
Objective: To investigate the effects of cinnamaldehyde on vascular endothelial function in aging rat model and its related mechanism. Methods: Sprague Dawley (SD) rats aged 24 months and HUVECs (14th passage) were established. Cinnamic aldehyde (10μM) was used to in vitro intervention. DHE staining and DAF -2DA staining was used to observe the effect of cinnamaldehyde on the level of superoxide anion and nitric oxide in carotid artery intima and HUVEC. The effects of cinnamaldehyde on acetylcholine-induced carotid artery endothelium-dependent vasodilatation and nitroglycerin-induced non-endothelium-dependent vasodilation were observed using a microvascular tensiometer. Western blotting was used to observe the phosphorylation of eNOS and the expression of Nrf2. Results: Cinnamic aldehyde incubation significantly decreased ROS levels in carotid intima and senescent HUVECs, increased phosphorylation of eNOS in HUVECs, increased NO levels, and improved acetylcholine-induced endothelium-dependent vasodilatation. Nitric glycerol-induced Non-endothelium-dependent diastolic function was not significantly affected; Nrf2 inhibitor javanicaol can significantly block the cinnamic aldehyde role. CONCLUSION: Cinnamaldehyde can reduce the senescence-related ROS production and increase the level of NO through the Nrf2 pathway to improve endothelium-dependent vasodilatation in aging rats.