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目的探讨替米沙坦对血管内皮细胞衰老是否存在有益的干预作用及可能的作用机制。方法健康大鼠分为成年组、老龄组、替米沙坦组,分析各组不同月龄大鼠主动脉衰老程度,_(gp)91~(phox)蛋白和mRNA表达与主动脉衰老程度的关系及替米沙坦是否存在有益的干预作用。体外培养的人脐静脉内皮细胞株(ECV-304)给予AngⅡ刺激以诱导细胞衰老,观察替米沙坦处理后细胞的衰老程度,进一步检测各组细胞_(gp)91~(phox)表达。结果老龄组大鼠主动脉呈现典型衰老改变,内皮细胞功能失调,伴有_(gp)91~(phox)的mRNA及蛋白表达上调;替米沙坦处理组主动脉衰老程度减轻,内皮功能改善。替米沙坦干预可降低AngⅡ诱导的ECV-304细胞的衰老改变,伴随_(gp)91~(phox)表达下调。结论替米沙坦可通过特异性拮抗AngⅡ的1型受体,改善增龄大鼠的主动脉内皮功能失调,延缓主动脉衰老改变。体外实验提示替米沙坦可抑制AngⅡ诱导的内皮细胞衰老,可能的途径是抑制了_(gp)91~(phox)的表达。
Objective To investigate the beneficial effects of telmisartan on the senescence of vascular endothelial cells and its possible mechanism. Methods Healthy rats were divided into adult group, aging group and telmisartan group. The changes of aorta aging, the expression of phox protein and mRNA in the rats with different ages were compared with those of aorta Relationship and telmisartan whether there is a beneficial intervention. The human umbilical vein endothelial cell line (ECV-304) cultured in vitro was stimulated with AngⅡ to induce cell senescence. The cell senescence after treatment with telmisartan was observed, and the expression of gp 91 ~ (phox) was further detected. Results The aorta of aging rats showed typical aging changes, dysfunction of endothelial cells, up-regulation of mRNA and protein expression of gp 91 ~ (phox), ameliorating senescence of the aorta and improvement of endothelial function in telmisartan-treated rats . Telmisartan can reduce the aging of ECV-304 cells induced by AngⅡ, with the decrease of (gp) 91 ~ (phox) expression. Conclusion Telmisartan can aorta endothelial dysfunction and delay aortic senescence by specifically antagonizing angiotensin Ⅱ type 1 receptor. In vitro experiments suggest that telmisartan can inhibit Ang Ⅱ-induced endothelial cell senescence, the possible pathway is to inhibit _ (gp) 91 ~ (phox) expression.