毛蕊异黄酮-丹参酮ⅡA调控内皮细胞功能参与高血压肾损害的机制研究

Mechanism study of Calycosin-TanshinoneⅡA on regulating endothelial cell function involved in hypertensive renal damage

目的:观察黄芪-丹参有效单体药对毛蕊异黄酮-丹参酮IIA延缓血管紧张素Ⅱ(AngⅡ)诱导大鼠肾动脉内皮细胞(RRAECs)损伤的作用机制。方法:以正常细胞为对照组,5×10^-7mol/L AngⅡ作用RRAECs 24h建立高血压肾损害模型,其余各组在AngⅡ基础上依次加入毛蕊异黄酮(1.5mg/L)、丹参酮ⅡA(3mg/L)、毛蕊异黄酮(3mg/L)+丹参酮ⅡA(3mg/L)、缬沙坦(10^-5mol/L),干预24h后,观察细胞增殖能力、凋亡率、活性氧(ROS)水平、内皮型一氧化氮合酶(eNOS)含量的变化。结果:与对照组比较,模型组细胞增殖能力显著降低(P<0.05),凋亡率升高(P<0.01),ROS生成增加(P<0.01),eNOS含量降低(P<0.05);与模型组比较,毛蕊异黄酮-丹参酮ⅡA显著提高RRAECs增殖能力和eNOS含量(P<0.01),降低细胞凋亡率(P<0.01),减少ROS生成(P<0.01)。结论:毛蕊异黄酮-丹参酮ⅡA改善AngⅡ诱导的RRAECs损伤,其机制可能与促进内皮细胞增殖,抑制细胞凋亡,减少ROS生成,提高eNOS水平等多因素相关。

Objective:To investigate the mechanism of Calycosin-TanshinoneⅡA,an effective monomer of Astragalus membranaceus-Salvia miltiorrhiza,in delaying angiotensinⅡ(AngⅡ)-induced rat renal artery endothelial cells(RRAECs)injury.Methods:Normal cells were used as control group,and RRAECs were treated with AngⅡat a concentration of 5×10^-7 mol/L for 24 h to establish a model of hypertensive renal damage.The other groups were respectively added with Calycosin(1.5 mg/L),TanshinoneⅡA(3 mg/L),Calycosin(3 mg/L)+TanshinoneⅡA(3 mg/L),Valsartan(10^-5 mol/L)after AngⅡadministration.The changes of cell proliferation,apoptosis rate,reactive oxygen species(ROS)and endothelial nitric oxide synthase(eNOS)levels in each group were observed and assessed.Results:Compared with the control group,cell proliferation and the level of eNOS in model group were significantly decreased(P<0.05,P<0.01),whereas the apoptosis rate and ROS level were remarkably increased(P<0.01).Calycosin-TanshinoneⅡA not only increased the proliferative ability and the level of eNOS but also reduced the apoptosis rate and ROS production in AngⅡ-induced RRAECs(P<0.01).Conclusion:Calycosin-TanshinoneⅡA could improve vascular endothelial cell injury induced by AngⅡwhich mechanism might be closely related to multiple factors such as enhancing cell proliferation,inhibiting apoptosis rate,reducing ROS production and upregulating the level of eNOS.