丹芪散对气虚血瘀型冠心病患者血管内皮功能的影响及网络药理学机制预测

Effects of Danqi San on Vascular Endothelial Function in Patients with Coronary Artery Disease of Qi-Deficiency and Blood-Stasis Type and Prediction of Network Pharmacological Mechanism

【目的】观察丹芪散对气虚血瘀型冠心病患者的临床疗效及对血管内皮功能与血管僵硬度的影响。【方法】将60例气虚血瘀型冠心病患者随机分为对照组和治疗组,每组各30例。对照组给予冠心病二级预防治疗,治疗组在对照组基础上配合丹芪散颗粒剂口服,治疗时间12周。观察2组患者治疗前后临床症状积分、血脂、踝肱指数(ABI)、肱踝脉搏波(PWV)、血清一氧化氮(NO)、内皮素1(ET-1)及不良反应的变化;再基于网络药理学的方法,对丹芪散改善气虚血瘀型冠心病患者血管内皮功能的作用进行理论论证。【结果】(1)治疗后,2组患者临床症状积分较治疗前均明显降低(P<0.01),且治疗组降低作用优于对照组(P<0.01)。(2)治疗后,2组患者低密度脂蛋白胆固醇(LDL-C)、胆固醇(TC)值较治疗前均明显降低(P<0.01),但2组间比较,差异无统计学意义(P>0.05)。(3)经过3个月的干预后,治疗组ABI值较治疗前升高(P<0.05),而对照组ABI值虽有所升高,但与治疗前比较,差异无统计学意义(P>0.05)。2组治疗后PWV值均下降(P<0.05或P<0.01),且治疗组降低作用优于对照组(P<0.01)。(4)治疗后,2组ET-1水平均较治疗前显著降低(P<0.01),且治疗组的降低作用优于对照组(P<0.01);治疗后,2组NO水平均较治疗前显著升高(P<0.01),且治疗组的升高作用优于对照组(P<0.01)。(5)2组不良反应发生率比较,差异无统计学意义(P>0.05)。(6)丹芪散可能通过影响流体剪切应力和动脉粥样硬化、细胞凋亡、p53信号通路、缺氧诱导因子1(HIF-1)信号通路、c型凝集素受体信号通路、ErbB信号通路、白细胞介素17(IL-17)信号通路和松弛素信号通路等多条通路改善冠心病患者的血管内皮功能。【结论】丹芪散可以改善气虚血瘀型冠心病患者的临床症状,改善血管内皮功能及血管僵硬度,这可能是其起效的作用机制。

Objective To observe the therapeutic effect of Danqi San for patients with coronary artery disease(CAD)of qi-deficiency and blood-stasis type,and the effects on vascular endothelial function and vascular stiffness.Methods Sixty CAD patients of qi-deficiency and blood-stasis type were randomly divided into control group and treatment group,30 cases in each group.The two groups received secondary prevention of CAD,additionally,the treatment group received oral use of Danqi San,the treatment lasting 12 weeks.The changes of clinical symptoms scores,blood lipids,ankle brachial index(ABI),pulse wave velocity(PWV),nitrous oxide(NO),endothelin 1(ET-1),and adverse reactions were observed in both groups before and after treatment.Moreover,the effect of Danqi San in improving vascular endothelial functions in CAD patients of qi-deficiency and blood-stasis type was verified by network pharmacology.Results(1)After treatment,the clinical symptoms scores in the two group were decreased(P<0.01 as compared with those before treatment),the decrease in the treatment group being superior to that in the control group(P<0.01).(2)After treatment,the low density lipoprotein cholesterol(LDL-C)and total cholesterol(TC)levels in the two groups were decreased(P<0.01 as compared with those before treatment),but the difference being insignificant in the two groups(P>0.05).(3)After 3 months of treatment,the ABI level in the treatment group was increased as compared with that before treatment(P<0.05),and the ABI level was also increased in the control group,but the difference being insignificant(P>0.05 as compared with that before treatment).The PWV level in the two groups was decreased(P<0.05 or P<0.01),the decrease in the treatment group being superior to that in the control group(P<0.01).(4)After treatment,the ET-1 level in the two group was decreased(P<0.01 as compared with those before treatment),the decrease in the treatment groups being superior to that in the control group(P<0.01).After treatment,the NO level in the two group was increased(P<0.01 as compared with those before treatment),the increase in the treatment groups being superior to that in the control group(P<0.01).(5)There was no significant difference in incidence rate of adverse reaction between the two groups(P>0.05).(6)Danqi San has possible effects on improving vascular endothelial functions in CAD patients by affecting multiple pathways such as fluid shear stress,atherosclerosis,cell apoptosis,p53 signaling pathway,hypoxia-inducible factor 1(HIF-1)signaling pathway,c-type lectin receptor signaling pathway,ErbB signaling pathway,interleukin 17(IL-17)signaling pathway and relaxin signaling pathway.Conclusion Danqi San is effective for improving the clinical symptoms of CAD patients of qi-deficiency and blood-stasis type,improving vascular endothelial function and vascular stiffness,which is possibly just the action mechanism.