基于血管内皮细胞损伤模型的丹参酮ⅡA治疗慢性心力衰竭的机制研究

摘要

Objective To study the effect of tanshinoneⅡA(TanⅡA)on the vascular endothelial cell(VEC)injury induced by the serum of the patients with chronic heart failure(CHF),and to explore the mechanism of action further. Methods The human umbilicus vein endothelial cells(CRL-1730)were injured by the 15% serum of the patients with CHF,then treated with different concentrations of TanⅡA(10μg/ml,20 μg/ml,40 μg/ml)for 24hours.The activity and the DNA damage of the VEC were determined.The level of the circulating endothelial cells(CEC),von willebrand factor(vWF)and thrombomodulin(TM)in the supernatant were also determined. Results Compare to the healthy control group,the activity of the VEC in the model group was decreasesd(P<0. 05),the percentage of tail DNA,tail extent and the olive tail moment were increased(P<0.05),the level of the CEC,VWF and TM were increased(P<0.05). Compare to the model group,20μg/ml and 40μg/ml TanⅡA can increase the activity of the VEC(P<0.05),reduce the cell DNA damage (P<0.05),all the three dose of TanⅡA can decrease the level of CEC,and 20μg/ml and 40μg/ml TanⅡA can decrease the level of vWF (P<0.05),and only the 40μg/ml TanⅡA can decrease the level of TM(P<0.05). Conclusion TanⅡA has a protective effect on the VEC by reducing the damage of the cell DNA maybe one of the mechanism in treating CHF.%目的：研究丹参酮ⅡA（TanⅡA）对慢性心力衰竭（CHF）患者血清损伤后的血管内皮细胞（VEC）的影响，探讨丹参酮ⅡA治疗CHF的作用机制。方法利用15%的CHF患者血清损伤正常培养的人脐静脉内皮细胞（CRL-1730），用不同浓度的TanⅡA（10、20、40μg/ml）作用于损伤后的细胞24 h，检测VEC的活性及细胞 DNA 的损伤；并检测细胞培养上清液中VEC损伤标志物循环内皮细胞数（CEC）、血管性假血友病因子（vWF）及血栓调节蛋白（TM）的水平变化。结果与健康对照组比较，模型组VEC细胞活性下降（P<0.05），尾部DNA%、彗星长及尾矩均上升（P<0.05），CEC、vWF及TM水平均上升（P<0.05）；与模型组比较，20μg/ml和40μg/ml的TanⅡA能增加内皮细胞的活性（P<0.05）；减轻DNA的损伤（P<0.01）；3个浓度的TanⅡA均可以减少CEC数（P<0.05）；20μg/ml和40μg/ml的TanⅡA可降低 vWF水平（P<0.05）；40μg/ml的TanⅡA可降低TM水平（P<0.05）。结论 TanⅡA能通过减轻CHF患者血清对内皮细胞的DNA损伤保护VEC，这可能是TanⅡA治疗CHF的作用机制之一。