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天津中医药大学 第二附属医院,天津 300250
王瑞华,博士,主治医师,从事中西医结合心血管疾病研究,E-mail: wangruihua2002@163.com
王保和,博士,主任医师,从事中医心血管疾病研究,E-mail: wbh3423@sina.com
收稿日期:2018-06-01,
纸质出版日期:2019-04-20
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王瑞华, 李艳芬, 邹爱英, 等. 黄连阿胶汤防治蒽环类化疗药物诱发心肌损伤的临床疗效及机制[J]. 中国实验方剂学杂志, 2019,25(8):20-27.
Rui-hua WANG, Yan-fen LI, Ai-ying ZUO, et al. Mechanism of Huanglian Ejiao Tang on Prevention and Treatment of Myocardial Injury Induced by Anthracycline Chemotherapy Drugs[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(8): 20-27.
王瑞华, 李艳芬, 邹爱英, 等. 黄连阿胶汤防治蒽环类化疗药物诱发心肌损伤的临床疗效及机制[J]. 中国实验方剂学杂志, 2019,25(8):20-27. DOI: 10.13422/j.cnki.syfjx.20190117.
Rui-hua WANG, Yan-fen LI, Ai-ying ZUO, et al. Mechanism of Huanglian Ejiao Tang on Prevention and Treatment of Myocardial Injury Induced by Anthracycline Chemotherapy Drugs[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(8): 20-27. DOI: 10.13422/j.cnki.syfjx.20190117.
目的:
2
观察黄连阿胶汤对于各类癌症化疗患者累积使用蒽环类化疗药物所导致的心肌损伤防治作用。
方法:
2
选择在天津中医药大学第二附属医院联合使用蒽环类药物化疗的各类癌症患者
21 d为1个周期,连续化疗3个周期后观察患者心脏毒性反应。选择符合中医心肾不交辨证标准的化疗患者共64例,随机分为治疗组和对照组,各32例。治疗组患者在维持原有化疗方案基础上,加用中药黄连阿胶汤为基本处方进行配合治疗,随证加减;对照组患者继续维持原有化疗方案,两组患者再连续化疗3周期。通过对比两组患者化疗后3
6周期心功能分级程度、心功能耐受性变化,以及心脏彩超,QTc间期,肌酸激酶同工酶(CK-MB),肌红蛋白(MYO),肌钙蛋白I(cTNI),氨基末端脑钠肽原(NT-pro-BNP)浓度数值的变化,并与肾上腺素(E),去甲肾上腺素(NE),血管紧张素Ⅱ(AngⅡ)水平比较,同时进行相关性分析。
结果:
2
中药治疗组化疗6个周期后心功能分级程度和6 min步行心功能耐受性均较化疗3周期后明显好转(
P
<
0.05),对照组则没有明显变化;治疗组血液CK-MB
cTNI
MYO
NT-pro-BNP水平较对照组明显下降(
P
<
0.05);心电图QTc间期治疗组较对照组明显下降(
P
<
0.05),心脏彩超指标动静脉血液流速比值(E/A),左室射血分数(LVEF)治疗组较对照组明显上升(
P
<
0.05),左室舒张末期内径(LVDd),左室收缩末期内径(LVDs)数值治疗组与对照组之间没有明显改变。两组化疗3
6周期后血液NE
E
AngⅡ水平比较,治疗组较对照组明显下降(
P
<
0.05);化疗后3至6周期血液NE
E
AngⅡ水平与CK-MB
cTNI
MYO
NT-pro-BNP水平变化值之间均存在直线正相关性;化疗6周期后,治疗组心血管事件发生率较化疗3周期后明显有所减少,对照组发生率则有所上升。
结论:
2
黄连阿胶汤通过补肾清心作用,可降低人体交感神经系统(SNS)和肾素-血管紧张素系统(RAS)兴奋性,抑制体内NE
E
AngⅡ释放水平,对累积使用蒽环类药物化疗患者的心脏毒性反应有一定的防治作用,在一定程度上能够抑制心肌损伤,改善心功能,减少心血管事件的发生。
Objective:
2
To observe the preventive and therapeutic effect of Huanglian Ejiao Tang on myocardial injury induced by anthracycline chemotherapeutic drugs in all kinds of cancer patients undergoing chemotherapy.
Method:
2
We chosen all kinds of cancer patients with combined use of anthracycline chemotherapy drugs in our hospital
21 days as one cycle. The cardiac toxicity reaction was observed after three continuous chemotherapy cycles. A total of 64 patients who met the dialectical criteria of "imbalance between heart-Yang and kidney-Yin" were randomly divided into treatment group (32 cases) and control group (32 cases). Patients in treatment group were treated with Chinese medicine Huanglian Ejiao Tang based on original chemotherapy regimen
adding and subtracting Chinese medical materials according to the symptoms. Patients in control group continued to maintain the original chemotherapy regimen
and both two groups of patients continued to receive 3 cycles of continuous chemotherapy. By comparing the cardiac function classification and cardiac function tolerance between the 3 cycles and 6 cycles of two groups of patients after chemotherapy; changes of echocardiography index
QTc interval
creatine kinase isoenzyme (CK-MB)
Myoglobin (MYO)
cardiac troponin I (cTNI)and nitrogenous terminal-pro-brain natriuretic peptide(NT-pro-BNP) concentration value were compared between two groups; and the concentrations of adrenaline (E)
norepinephrine (NE) and angiotensin Ⅱ(AngⅡ) were observed and compared; meanwhile
the correlation analysis was carried out at the same time.
Result:
2
After 6 cycles of chemotherapy in Chinese medicine treatment group
degree of cardiac function classification and the 6 minute walking heart function tolerance were significantly better than those at the 3 cycles of chemotherapy (
P
<
0.05)
but there was no significant change in control group; the concentrations of CK-MB
cTNI
MYO and NT-pro-BNP in treatment group were significantly lower than those in control group(
P
<
0.05)
and the electrocardiogram QTc interval in the treatment group was significantly lower than that in the control group (
P
<
0.05); echocardiography indexes E/A ratio and left ventricular ejective fraction (LVEF) value in the treatment group were significantly higher than those in control group (
P
<
0.05). There were no significant changes in left ventricular end-systolic diameter (LVDd) and left ventricular end-systolic diameter (LVDs) between the treatment and the control group. After 3 cycles and 6 cycles of chemotherapy
the blood NE
E and AngⅡ concentrations in the treatment group were significantly lower than those in the control group (
P
<
0.05). There were positive linear correlation in concentration changes of blood NE
E and AngⅡ as well as the concentration changes of CK-MB
cTNI
MYO and NT-pro-BNP between 3 cycles and 6 cycles after chemotherapy. After 6 cycles of chemotherapy
the incidence of cardiovascular events in the treatment group was significantly lower than that in the 3 cycles of chemotherapy
while the incidence in control group was increased.
Conclusion:
2
Huanglian Ejiao Tang can reduce the excitability of the symppthetic nervous system (SNS) and renin-angiotensin system(RAS) in human body and inhibit the release level of NE
E and AngⅡ by effect of "invigorating the kidney and clearing the heart" . It has a certain preventive and treatment effect on the cardiac toxicity of patients with the cumulative use of anthracycline chemotherapy. To a certain extent
it can inhibit myocardial injury
improve cardiac function and reduce the incidence of cardiovascular events.
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