桂皮醛上调Nrf2改善衰老大鼠血管内皮功能障碍

Cinnamaldehyde Improved Aging-related Endothelium Dysfunction through Up-regulating Nrf2

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 explore the effect and the mechanism of Cinnamaldehyde （CA） on aging rats endothelium dependent re- laxation function. Methods： Natural aging Sprague Dawley （SD） rat model and aging human umbilical vein endothelial cells （HUVECs） were constructed and used in this study. DHE stainning and DAF-2DA staining were used to detect Reactive oxygen species （ROS） and Nitric oxide （NO） levels respectively. Endothelium dependent relaxation （EDR） induced by Acetylcholine （ACh） and endothelium inde- pendent relaxation （IDR） induced by Nitroglycerin （NTG） were observed by Wire myograph. Expression of Nuclear factor E2-related factor 2（Nrf2 ）and the phosphorylation of eNOS were detected by western blotting. Results： Treatment with CA decreased ROS level and promoted eNOS phosphorylation, thus increased NO level, improved EDR of carotid arteries in aging rat. CA did not affect the IDR of carotid arteries in aging rats. Pretreatment with Nrf2 inhibitor, brusatol reversed the effects of CA. Conclusion： CA attenuated the ROS level, increased the NO level hence improved the EDR is depended Nrf2 activation.