炙甘草汤辨证论治病毒性心肌炎的临床研究
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摘要
[目的]探讨炙甘草汤辨证论治病毒性心肌炎(气阴两虚证)的临床疗效及作用机制。[方法]采用平行、随机、对照试验方案,选择符合病毒性心肌炎(气阴两虚证)诊断标准的患者76例,随机分为治疗组和对照组各38例。对照组予常规治疗,治疗组在常规治疗基础上联合炙甘草汤口服,疗程4周。分别记录两组患者治疗前、后中医证候积分、心电图及心脏彩超检查结果;检测血浆N末端-B型利钠肽前体(N-terminal prohormone of brain natriuretic peptide,NT-proBNP)、肌酸激酶(creatine kinase,CK)、肌酸激酶同工酶(creatine kinase-MB,CK-MB)、肌钙蛋白I(cardiac troponin I,cTnI)、高敏C反应蛋白(hypersensitive C-reactive protein,hs-CRP)、白介素-6(interleukin-6,IL-6)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、丙二醛(malonaldehyde,MDA)、超氧化物歧化酶(superoxide dismutase,SOD)含量,并记录相关安全性指标(三大常规、肝肾功能等)及不良反应。[结果]治疗组总有效率为92.10%,对照组为73.68%,治疗组优于对照组(P<0.05),治疗组中医证候积分较对照组降低更明显(P<0.05)。治疗后两组患者NT-proBNP、CK、CK-MB、cTnI均较治疗前明显降低(P<0.05),且治疗组CK、CK-MB下降幅度优于对照组(P<0.05)。同时,治疗后两组患者血浆hs-CRP、TNF-α、IL-6、MDA含量均较治疗前显著降低(P<0.05),且治疗组下降幅度均大于对照组(P<0.05);SOD含量均较治疗前升高,治疗组升高幅度大于对照组(P<0.05)。[结论]常规治疗基础上加用炙甘草汤辨治病毒性心肌炎(气阴两虚证)疗效显著,可显著改善患者的临床症状,减少心肌细胞损伤,促进心肌细胞修复,其作用机制可能包括抑制体内炎症和抗氧化应激两个方面。
[Objective] To investigate clinical effect and mechanism of Zhigancao Decoction on viral myocarditis(VMC) of Qi-Yin deficiency. [Methods] In a parallel, randomized trial, 76 patients with VMC(syndrome of Qi-Yin deficiency) were enrolled and divided into treatment group and control group, 38 cases in each group. Patients in control group were given routine treatments, while patients in treatment group were given Zhigancao Decoction combined with routine treatments.The TCM syndrome scores, electrocardiograms, echocardiography, N-terminal prohormone of brain natriuretic peptide(NT-proBNP), creatine kinase(CK), creatine kinase-MB(CK-MB), cardiac troponin I(cTnI), hypersensitive C-reactive protein(hs-CRP), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), malonaldehyde(MDA)and superoxide dismutase(SOD) were recorded respectively before and 4 weeks after treatment, as well as security indicators of blood, urine and excrement tests, liver and kidney functions, and adverse events. [Results] Four weeks after treatment, the total effective rate of treatment group was 92.10%, while that of control group was 73.68%, which suggested that treatment group worked better( P<0.05); TCM syndrome scores of treatment group were significantly lower than those of control group( P<0.05). After treatments, the level of NT-proBNP, CK, CK-MB and cTnI were lower than before in both groups(P<0.05). In addition, CK and CK-MB in treatment group decreased significantly compared with control group(P<0.05). The level of hs-CRP, TNF-α, IL-6 and MDA were lower than before in both groups(P<0.05), meanwhile, those in treatment group were decreased significantly compared with control group(P<0.05). Besides, the level of SOD was increased in both groups(P<0.05), but increased significantly in treatment group(P<0.05).[Conclusion] The effect of Zhigancao Decoction combined with routine treatments on VMC(syndrome of Qi-Yin deficiency)was remarkable. Zhigancao Decoction was effective in improving patients' clinical symptoms and reducing myocardial cell damages.The mechanism of action might be related to inhibition of inflammatory responses and anti-oxidative stress reactions.
[Objective] To investigate clinical effect and mechanism of Zhigancao Decoction on viral myocarditis(VMC) of Qi-Yin deficiency. [Methods] In a parallel, randomized trial, 76 patients with VMC(syndrome of Qi-Yin deficiency) were enrolled and divided into treatment group and control group, 38 cases in each group. Patients in control group were given routine treatments, while patients in treatment group were given Zhigancao Decoction combined with routine treatments.The TCM syndrome scores, electrocardiograms, echocardiography, N-terminal prohormone of brain natriuretic peptide(NT-proBNP), creatine kinase(CK), creatine kinase-MB(CK-MB), cardiac troponin I(cTnI), hypersensitive C-reactive protein(hs-CRP), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), malonaldehyde(MDA)and superoxide dismutase(SOD) were recorded respectively before and 4 weeks after treatment, as well as security indicators of blood, urine and excrement tests, liver and kidney functions, and adverse events. [Results] Four weeks after treatment, the total effective rate of treatment group was 92.10%, while that of control group was 73.68%, which suggested that treatment group worked better( P<0.05); TCM syndrome scores of treatment group were significantly lower than those of control group( P<0.05). After treatments, the level of NT-proBNP, CK, CK-MB and cTnI were lower than before in both groups(P<0.05). In addition, CK and CK-MB in treatment group decreased significantly compared with control group(P<0.05). The level of hs-CRP, TNF-α, IL-6 and MDA were lower than before in both groups(P<0.05), meanwhile, those in treatment group were decreased significantly compared with control group(P<0.05). Besides, the level of SOD was increased in both groups(P<0.05), but increased significantly in treatment group(P<0.05).[Conclusion] The effect of Zhigancao Decoction combined with routine treatments on VMC(syndrome of Qi-Yin deficiency)was remarkable. Zhigancao Decoction was effective in improving patients' clinical symptoms and reducing myocardial cell damages.The mechanism of action might be related to inhibition of inflammatory responses and anti-oxidative stress reactions.
引文
[1]高见书,汪芳.心电图表现酷似急性冠状动脉综合征的急性病毒性心肌炎20例临床分析[J].中国动脉硬化杂志,2015,23(3):307-309.
[2]丛超,郭义山,王东.病毒性心肌炎发病机制的研究进展[J].医学综述,2017,23(15):2948-2953.
[3]中华心血管病杂志编辑委员会心肌炎心肌病对策专题组.关于成人急性病毒性心肌炎诊断参考标准和采纳世界卫生组织及国际心脏病学会联合会工作组关于心肌病定义和分类的意见[J].中华心血管病杂志,1999,27(6):405-407.
[4]中华中医药学会.中医内科常见病诊疗指南(西医疾病部分)病毒性心肌炎[J].中国中医药现代远程教育,2011,9(18):148-150.
[5]张军平,吕仕超,朱亚萍,等.病毒性心肌炎中医证候学专家问卷分析[J].中华中医药学刊,2011,29(9):1942-1944.
[6]郑筱萸.中药新药临床研究指导原则[M].北京:中国医药科技出版社,2002:46-51.
[7]张鑫.112例成人急性心肌炎的临床分析[D].长春:吉林大学,2017:4.
[8]叶天士,薛雪.温热论湿热论[M].张志斌,整理.北京:人民卫生出版社,2007:15.
[9]张介宾.景岳全书[M].李继明,王大淳,整理.北京:人民卫生出版社,2007:413.
[10]Cen Z,Guo Y,Kong Q,et al.IL-10-prouducing B cells involved in the pathogenesis of Coxsackie virus B3-induced acute viral myocarditis[J].Int J Clin Exp Pathol,2015,8(1):830-835.
[11]Sinnecker D,Laugwitz K L,Moretti A.Extending human induced pluripotent stem cell technology to infectious diseases:new model for viral myocarditis[J].Cir Res,2014,115(6):537-539.
[12]Piao Y L,Liang X C.Astragalus membrananceus injection combined with conventional treatment for viral myocarditis:A systematic review of randomized controlled trails[J].Chin J Integr Med,2014,20(10):787-791.
[13]Wang D,Li T,Cui H,et al.Analysis of the indicating value of cardiac troponin I,tumor necrosis factor-α,interleukin-18,mir-1 and mir-146b for viral myocarditis among children[J].Cell Physiol Biochem,2016,40(6):1325-1333.
[14]Zhou L,He X,Gao B,et al.Inhibition of histone deacetylase activity aggravates coxsackievirus B3-induced myocarditis by promoting viral replication and myocardial apoptosis[J].J Virol,2015,89(20):10512-10523.
[15]顾熙东,章晓鹰,徐金龙,等.病毒性心肌炎患者血清CK-MB、hs-CRP、IL-35及cTnI水平的表达[J].现代生物医学进展,2017,17(6):1099-1101.
[16]曹永,徐侠,张培影.五参二连颗粒对病毒性心肌炎病人血清IL-6、TNF-α及cTnI水平的影响[J].中西医结合心脑血管病杂志,2016,14(19):2213-2215.
[17]李忠,张培华.小檗碱通过Toll样受体4/核因子κB信号通路对小鼠病毒性心肌炎发挥保护作用[J].中国动脉硬化杂志,2017,25(3):250-253.
[18]刘艳丽,伍伟锋,薛贻敏,等.TGF-β、IL-6和IL-17在小鼠病毒性心肌炎中的表达[J].实用医学杂志,2013,29(13):2097-2099.
[19]李琳琳,高晓峰,付亮.急性病毒性心肌炎患儿血中VCAM-1及IL-6的浓度变化及其相关性研究[J].内蒙古医科大学学报,2014,36(1):29-34.
[20]Abrar S,Ansari M J,Mittal M,et al.Predictors of mortality in paediatric myocarditis[J].J Clin Diagn Res,2016,10(6):12-16.
[21]赵振霞,赵振敏,李彤.黄芪注射液对病毒性心肌炎患者氧化应激和炎性反应影响[J].中国实验方剂学杂志,2015,21(23):176-179.
[22]赵晓宇,曹妍,孙鹤,等.氧化应激与病毒性心肌炎[J].现代生物医学进展,2015,15(4):785-787.
[2]丛超,郭义山,王东.病毒性心肌炎发病机制的研究进展[J].医学综述,2017,23(15):2948-2953.
[3]中华心血管病杂志编辑委员会心肌炎心肌病对策专题组.关于成人急性病毒性心肌炎诊断参考标准和采纳世界卫生组织及国际心脏病学会联合会工作组关于心肌病定义和分类的意见[J].中华心血管病杂志,1999,27(6):405-407.
[4]中华中医药学会.中医内科常见病诊疗指南(西医疾病部分)病毒性心肌炎[J].中国中医药现代远程教育,2011,9(18):148-150.
[5]张军平,吕仕超,朱亚萍,等.病毒性心肌炎中医证候学专家问卷分析[J].中华中医药学刊,2011,29(9):1942-1944.
[6]郑筱萸.中药新药临床研究指导原则[M].北京:中国医药科技出版社,2002:46-51.
[7]张鑫.112例成人急性心肌炎的临床分析[D].长春:吉林大学,2017:4.
[8]叶天士,薛雪.温热论湿热论[M].张志斌,整理.北京:人民卫生出版社,2007:15.
[9]张介宾.景岳全书[M].李继明,王大淳,整理.北京:人民卫生出版社,2007:413.
[10]Cen Z,Guo Y,Kong Q,et al.IL-10-prouducing B cells involved in the pathogenesis of Coxsackie virus B3-induced acute viral myocarditis[J].Int J Clin Exp Pathol,2015,8(1):830-835.
[11]Sinnecker D,Laugwitz K L,Moretti A.Extending human induced pluripotent stem cell technology to infectious diseases:new model for viral myocarditis[J].Cir Res,2014,115(6):537-539.
[12]Piao Y L,Liang X C.Astragalus membrananceus injection combined with conventional treatment for viral myocarditis:A systematic review of randomized controlled trails[J].Chin J Integr Med,2014,20(10):787-791.
[13]Wang D,Li T,Cui H,et al.Analysis of the indicating value of cardiac troponin I,tumor necrosis factor-α,interleukin-18,mir-1 and mir-146b for viral myocarditis among children[J].Cell Physiol Biochem,2016,40(6):1325-1333.
[14]Zhou L,He X,Gao B,et al.Inhibition of histone deacetylase activity aggravates coxsackievirus B3-induced myocarditis by promoting viral replication and myocardial apoptosis[J].J Virol,2015,89(20):10512-10523.
[15]顾熙东,章晓鹰,徐金龙,等.病毒性心肌炎患者血清CK-MB、hs-CRP、IL-35及cTnI水平的表达[J].现代生物医学进展,2017,17(6):1099-1101.
[16]曹永,徐侠,张培影.五参二连颗粒对病毒性心肌炎病人血清IL-6、TNF-α及cTnI水平的影响[J].中西医结合心脑血管病杂志,2016,14(19):2213-2215.
[17]李忠,张培华.小檗碱通过Toll样受体4/核因子κB信号通路对小鼠病毒性心肌炎发挥保护作用[J].中国动脉硬化杂志,2017,25(3):250-253.
[18]刘艳丽,伍伟锋,薛贻敏,等.TGF-β、IL-6和IL-17在小鼠病毒性心肌炎中的表达[J].实用医学杂志,2013,29(13):2097-2099.
[19]李琳琳,高晓峰,付亮.急性病毒性心肌炎患儿血中VCAM-1及IL-6的浓度变化及其相关性研究[J].内蒙古医科大学学报,2014,36(1):29-34.
[20]Abrar S,Ansari M J,Mittal M,et al.Predictors of mortality in paediatric myocarditis[J].J Clin Diagn Res,2016,10(6):12-16.
[21]赵振霞,赵振敏,李彤.黄芪注射液对病毒性心肌炎患者氧化应激和炎性反应影响[J].中国实验方剂学杂志,2015,21(23):176-179.
[22]赵晓宇,曹妍,孙鹤,等.氧化应激与病毒性心肌炎[J].现代生物医学进展,2015,15(4):785-787.