肾素(前体)受体在高糖诱发的内皮细胞舒缩功能障碍中的作用及机制

The Roles and Mechanisms of the Prorenin Receptor in Hyperglycemia Mediated Endothelial Dysfunction

目的探讨高糖对内皮细胞舒缩功能障碍等损害过程中是否有肾素(前体)受体((P)RR)的过度激活,并探讨其机制。方法体外培养人脐静脉内皮细胞,分别以不同浓度的葡萄糖(15、30mmol/L)干预细胞24h、48h后收取细胞,用分子生物学方法测定(P)RR以及反映血管舒缩功能的生物标记物蛋白和mRNA的表达,以siRNA的方法抑制(P)RR的表达后,观察葡萄糖对内皮细胞上述作用的改变,进一步分析其机制。结果高糖显著上调内皮细胞(P)RR的蛋白和mRNA表达;同时上调内皮素1(ET-1)的表达,抑制一氧化氮(NO)的合成。(P)RR-siRNA虽能抑制高糖引起的ET-1mRNA表达增高,但不抑制其蛋白表达。(P)RR-siRNA显著抑制高糖引起的NO降低。高糖抑制内皮型一氧化氮合酶(eNOS)的表达,增加非对称性二甲基精氨酸(ADMA)的合成,(P)RRsiRNA能显著抑制高糖对eNOS和ADMA的影响。结论高糖能够激活内皮细胞(P)RR的表达;(P)RR可能通过ADMA/eNOS通路介导了高糖诱发的血管内皮舒缩功能障碍。

Aim To detect the role and mechanism of excessive activation of（pro）renin receptor（（P）RR） in hyperglycemia induced endothelial dysfunction.Methods Endothelial cells were cultured in vivo and intervened with glucose of different concentrations（15,30 mmol / L） and different courses（24 h,48 h）.The mRNA and protein levels of（P） RR and markers reflecting vascular function were measured.（P） RR expression was then inhibited by siRNA to observe the corresponding changes mentioned before.Results Both protein and mRNA expression of endothelial cells was significantly increased by hyperglycemia.Hyperglycemia upregulated the expression of endothelin-1（ET-1） and inhibited the synthesis of nitric oxide（NO）.（P） RR-siRNA couldn＇t inhibit the expression of ET-1 protein,although it could inhibit its mRNA elevation in hyperglycemia.（P） RR-siRNA could significantly inhibitNO reduction in hyperglycemia.Hyperglycemia inhibited the expression of endothelial nitric oxide synthase（eNOS） and provoked the synthesis of asymmetric dimethylarginine（ADMA）,which could be significantly inhibited by（P） RR-siRNA.Conclusions Hyperglycemia activated（P） RR expression in endothelial cells.Hyperglycemia induced vascular endothelial dysfunction might be mediated by（P） RR via ADMA / eNOS pathway.