二十五味肺病丸改善斑马鱼微血管功能障碍及机制的探究

Effect of Ershiwuwei Feibing Pills on microvessel dysfunction and underlying mechanism in zebrafish

[目的]观察二十五味肺病丸是否能够改善微血管功能障碍并探究其潜在机制。[方法]利用花生四烯酸诱导建立斑马鱼血栓模型,检测二十五味肺病丸给药组和对照组斑马鱼心输出量和血流速度;用辛伐他汀诱导建立斑马鱼微血管缺失模型,计算斑马鱼肠下血管面积和斑马鱼体节间血管直径;给予普纳替尼诱发斑马鱼血管内皮损伤模型,观察尾静脉血栓形成情况,以评价二十五味肺病丸对微血管功能的影响。[结果]与对照组相比,二十五味肺病丸给药组(27.8 mg/L)心输出量显著性增加(0.11 vs 0.19 nL/s,P<0.05),血流速度显著增加(398 vs 693μm/s,P<0.001),肠下血管面积增加(19335 vs 25041像素,P<0.05),微血管再生促进作用增强;同样,给予二十五味肺病丸处理后(83和250μg/mL),斑马鱼节间血管直径明显增大(8.7 vs 11.5 vs 11.8像素,P<0.001),血栓发生率显著下降。[结论]二十五味肺病丸可以改善微血管功能障碍,其可能是通过改善微血管血流动力学作用、减少血管内皮损伤、促进内皮再生和减少血栓生成实现。

[Objective]To investigate whether Ershiwuwei Feibing Pills(EFP)could mitigate microvessel dysfunction and the underlying mechanism.[Methods]Zebrafish was treated with arachidonic acid to induce models of thrombosis and zebrafish heart output and blood flow velocity were detected in zebrafish models with or without treatment of EFP.Simvastatin was used to induce microvascular defect and the vascular area of the zebrafish intestine and the intervascular diameter were calculated.Similarly,ponatinib was adopted to cause vascular endothelial injury and the thrombus in the tail vein was observed with microscope.[Results]Compared with the control group,the EFP group(27.8 mg/L)group had a significant increase in cardiac output(0.11 nL/s vs 0.19 nL/s,P<0.05),and a significant increase in blood flow velocity(398μm/s vs 693μm/s,P<0.001).The area of intestinal blood vessels was increased(19335 pixels vs 25041 pixels,P<0.05),and the promotion of microvascular regeneration was enhanced.Furthermore,after treatment with EFP(83 and 250μg/mL),the diameter of zebrafish internode vessels increased significantly(8.7 vs 11.5 vs 11.8 pixels,P<0.001),and the incidence of thrombosis decreased significantly.[Conclusion]EFP can improve microvessel dysfunction,which may result from improving microvascular hemodynamics,reducing vascular endothelial damage and promoting endothelial regeneration and thrombosis.