神经酰胺和p53在AngⅡ诱导内皮细胞凋亡过程中的作用  

The correlation between ceramide and p53 in endothelial cells apoptosis induced by AngⅡ

作　　者：杨丽霞[1] 杨栋[1] 郭瑞威[1] 沈珠甫[1] 石燕昆[1] 齐峰[1] 王先梅[1] 

机构地区：[1]成都军区昆明总医院心内科,昆明650032

出　　处：《解放军医学杂志》2007年第8期830-831,838,共3页Medical Journal of Chinese People's Liberation Army

基　　金：云南省自然科学基金(2006C0059M)

摘　　要：目的探讨AmgⅡ诱导内皮细胞凋亡过程中神经酰胺和p53的作用及相互关系。方法体外培养脐静脉内皮细胞,分别用血管紧张素Ⅱ1型受体(AT1)拮抗剂氯沙坦、血管紧张素Ⅱ2型受体(AT2)拮抗剂PD123319、神经酰胺合成酶抑制剂烟曲霉素B1 (FB1)、p53抑制剂PFT-α预处理细胞,再加入AngⅡ,24h后与对照组(用双蒸水预处理细胞)比较,观察细胞凋亡情况,RT-PCR和Western blot检测各组p53表达情况。结果PD123319和FB1能显著抑制AngⅡ诱导的内皮细胞凋亡,而氯沙坦和PFT-α则不能抑制AngⅡ诱导的内皮细胞凋亡。FB1和PFT-α可以抑制p53的mRNA和蛋白表达。结论AngⅡ通过AT2受体和神经酰胺诱导内皮细胞凋亡。神经酰胺在AngⅡ诱导的内皮细胞凋亡过程中起重要作用,且可能经过p53诱导凋亡。Objective Angiotensin （AngⅡ） is an important proinflammatory mediator in the cardiovascular system. The present study is aimed at investigating the correlation between ceramide and p53 and apoptosis of human umbilical endothelial cells induced by Ang Ⅱ, Methods Human umbilical endothelial cells were cultured in vitro and treated with AngⅡ alone or in combination with Losartan （an inhibitor of AT1）, PD123319 （an inhibitor of AT2）, FB1 （an inhibitor of ceramidase）, PFT-α （an inhibitor of p53）, respectively. The apoptosis of cells was detected with TUNEL, and p53 expression at protein and mRNA was assessed with Western blotting and reverse transcription-polymerase chain reaction （RT-PCR）. Results Compared to Angα group, PD123319 and FB1 could inhibit endothelial cells apoptosis induced by AngⅡ at 24h; but Losartan and PFT-α could not. Compared to the control group, no statistical difference existed between PD123319 and FB1, but it did exist between Losartan and PFT-α FB1 and PFT-α down-regulated the p53 expression at the protein and mRNA levels. Conclusion In the process of apoptosis induced by AngⅡ, AngⅡ can induce the activation of ceramide by binding with AT2. AT2 and Ceramide play a key role in the endothelial cells apoptosis induced by AngⅡ. Ceramide may be situated in the upper stream of p53 and induce the apoptosis by p53 pathway.

关 键 词：神经酰胺类 P53蛋白质 血管紧张素类 内皮细胞 细胞凋亡 

分 类 号：R543[医药卫生—心血管疾病]