麝香通心滴丸对缺血性心力衰竭心肌纤维化和血管再生的影响机制

Influence Mechanism of Myocardial Fibrosis and Vascular Regeneration of Shexiang Tongxin Pills to Syndrome of Qi Deficiency and Blood Stasis in Ischemic Heart Failure

目的:评价麝香通心滴丸治疗缺血性心力衰竭(IHF)气虚血瘀证的临床疗效及对心肌纤维化和血管再生的影响机制。方法:将140例患者按1∶1随机数字表法分为对照组和观察组各70例,对照组脱落、失访3例,剔除1例,完成66例;观察组脱落、失访4例,剔除1例,完成65例。两组患者参照指南给予综合治疗措施。对照组口服麝香通心滴丸模拟药,2丸/次,3次/d。观察组口服麝香通心滴丸,2丸/次,3次/d。均连续治疗24周。进行治疗前后超声心动图检查,测量左心室射血分数(LVEF),心输出量(CO),左室舒张末期内径(LVEDd),左室后壁厚度(LVPW),左室质量指数(LVMI)和左室重构指数(LVRI);进行治疗前后6 min步行试验(6 MWT),Lee氏心衰评分、气虚血瘀证评分和明尼苏达心力衰竭生活质量调查表(MLHFQ)评分;检测治疗前后N末端B型利钠肽原(NT-proBNP),转化生长因子-β1(TGF-β1),可溶性ST2(sST2),基质金属蛋白酶-2(MMP-2),基质金属蛋白酶抑制因子-2(TIMP-2),胰岛素样生长因子-1(IGF-1),血管内皮生长因子(VEGF),血管生成素1(Ang1)和血管生成素2(Ang2)。进行安全性评价。结果:观察组临床疗效总有效率为90.77%(59/65),高于对照组的74.24%(49/66)(χ^(2)=6.179,P<0.05);观察组LVEF,CO和LVRI均高于对照组(P<0.05),LVEDd,LVPW,LVMI均低于对照组(P<0.05);观察组6 MWT多于对照组(P<0.01),Lee氏心衰、气虚血瘀证和MLHFQ评分均低于对照组(P<0.01);观察组NT-proBNP,TGF-β1,sST2,MMP-2水平均低于对照组(P<0.01),TIMP-2水平高于对照组(P<0.01);观察组IGF-1,VEGF,Ang1水平均高于对照组(P<0.01),Ang2水平低于对照组(P<0.01)。没有发现服用麝香通心滴丸相关不良反应。结论:在西医常规治疗的基础上,给予麝香通心滴丸治疗IHF气虚血瘀证患者,可通过影响心肌纤维化和血管再生因子,改善心室重构,提高患者心脏功能,减轻临床症状,增加患者的运动耐量和生活质量,有着较好的临床疗效与安全性。

Objective: To discuss clinical effect of Shexiang Tongxin pills to syndrome of Qi deficiency and blood stasis in ischemic heart failure(IHF)and to study the mechanism to myocardial fibrosis and vascular regeneration. Method: One hundred and forty patients were randomly divided into observation group(70 cases)and control group(70 cases)with the same cases. 66 patients in control group finish the therapy(3 patients fall off or lost visit,1 were eliminated). 65 patients in observation group completed the therapy(4 patients were falling off,1 were eliminated). Both groups patients got combined treatment according to the guiding. Patients in control group got simulated medicine of Shexiang Tongxin pills,2 pills/time,3 times/day. Patients in observation group got Shexiang Tongxin pills,2 pills/time,3 times/day. The treatment was continued for 24 weeks. Before and after treatment,the left ventricular ejection fraction(LVEF),cardiac output(CO),end diastolic diameter(LVEDd),left posterior wall thickness(LVPW),left ventricular mass index(LVMI)and left ventricular remodeling index(LVRI)were measured by echocardiography. And scores of six minute walking test(6 MWT),Lee’s heart failure score,Qi deficiency and blood stasis syndrome score and Minnesota Heart Failure Quality of life questionnaire(MLHFQ)were graded. And levels of N-terminal B-type natriuretic peptide(NT-pro BNP),transforming growth factor-β1(TGF-β1),soluble ST2(s ST2),matrix metalloproteinase-2(MMP-2),matrix metalloproteinase inhibitor-2(TIMP-2),insulin-like growth factor-1(IGF-1),vascular endothelial growth factor(VEGF),angiopoietin1(Ang1)and angiopoietin2(Ang2),and the safety was evaluated. Result: The total clinical effect in observation group was 90.77%(59/65)higher than74.24%(49/66)in control group(χ^(2)=6.179,P<0.05). Levels of LVEF,CO,LVRI,6 MWT,TIMP-2,IGF-1,VEGF and Ang1 were higher than those in control group(P<0.01). And levels of LVEDd,LVPW and LVMI were lower than those in control group(P<0.05),levels of NT-pro BNP,TGF-β1,s ST2,MMP-2 and Ang2 were lower than those in control group(P<0.01),scores of Lee’s heart failure score,Qi deficiency and blood stasis syndrome score and MLHFQ were lower than those in control group(P<0.01). Besides,there was no adverse reactions caused by Shexiang Tongxin dropping pills. Conclusion: On the basis of conventional western medicine treatment,Shexiang Tongxin drop pills can improve the ventricular remodeling,improve the heart function,reduce the clinical symptoms,increase the exercise tolerance and quality of life of the patients by affecting the myocardial fibrosis and vascular regeneration factor,which has better clinical efficacy and safety.