血管紧张素受体1在血管紧张素Ⅱ诱导人星形胶质细胞老化中的作用

Role of AT1 in Ang Ⅱ-induced astrocyte senescence

目的通过体外细胞实验研究,探讨血管紧张素受体1在血管紧张素Ⅱ诱导人星形胶质细胞活性氧产生和细胞老化中的作用。方法人星形胶质细胞随机分为三组:血管紧张素Ⅱ+Cand(坎地沙坦)组和血管紧张素Ⅱ+tempol组。血管紧张素Ⅱ组是用100nM血管紧张素Ⅱ刺激人星形胶质细胞3天,血管紧张素Ⅱ+Cand组和血管紧张素Ⅱ+tempol组先用血管紧张素受体1阻滞剂坎地沙坦(100nM)和氧自由基清除剂tempol(3mM)预处理,再用100nM血管紧张素Ⅱ刺激人星形胶质细胞3天,利用β半乳糖苷酶染色评估细胞老化。不同剂量(0、1nM、10nM、100nM、1000nM和1000nM+坎地沙坦)的血管紧张素Ⅱ刺激人星形胶质细胞30min,DHE染色评估细胞内活性氧产生。结果血管紧张素Ⅱ引起人星形胶质细胞DHE染色表达增多和β半乳糖苷酶染色细胞增多。利用血管紧张素受体1阻滞剂坎地沙坦和氧自由基清除剂tempol预处理逆转了血管紧张素Ⅱ引起的星形胶质细胞老化。结论血紧张素Ⅱ是通过血管紧张素受体1和超氧阴离子产生引起星形胶质细胞的老化。

Objective To determine the role of angiotensin type 1 receptors in the angiotensin Ⅱ-induced reactive oxygen species production and the cellular senescence in cultured human astrocytes. Methods Oxidative fluorescent dihydroethidium and β-galactosidase staining were used to evaluate intracellular production of superoxide anion and cell senescence, respectively. Astrocytes were pretreated with candesatan （100 nM） for 3 h or tempol （3 mM） for 30 min before incubation with Ang Ⅱ （100 nM）, respectively. ResultsThe staining of dihydroethidium was increased by angiotensin Ⅱ in human astrocytes. Angiotensin Ⅱ dose-dependently induced the increase in β-galactosidase staining. Moreover, pretreatment with angiotensin type 1 receptor blocker candesatan, and antioxidant tempol, abolished angiotensin Ⅱ-induces astrocyte senescence. Conclusion Angiotensin Ⅱ induced astrocyte senescence via angiotensin type 1 receptors and superoxide anion production.