加味丹参饮对慢性心力衰竭大鼠心脏功能和血清炎性因子IL-6及TNF-α的影响
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摘要
目的:探讨加味丹参饮对慢性心力衰竭大鼠心脏功能、血清炎性因子白细胞介素6 (IL-6)和肿瘤坏死因子α(TNF-α)的影响,阐明加味丹参饮治疗慢性心力衰竭的机制。方法:SD大鼠随机分为空白对照组,心力衰竭模型组,卡托普利组,低、中和高剂量加味丹参饮组。腹腔注射阿霉素溶液制备慢性心力衰竭大鼠模型,连续给药4周,采用超声心动图检测各组大鼠左室射血分数(LVEF);利用呼吸机测定各组大鼠的心率(HR)、心排出量(CO)、颈动脉收缩压(SBP)、颈动脉舒张压(DBP)、左心室舒张期末压(LVEDP)、左心室收缩压(LVSP)和左心室压变化最大上升/下降速率(±dp/dtmax)等相关血流动力学参数,评价大鼠心脏功能。利用酶联免疫吸附法(ELISA法)检测大鼠血清中IL-6和TNF-α水平。取各组大鼠心和肺组织,计算心和肺脏指数。结果:与空白对照组比较,模型组,卡托普利组,低、中和高剂量加味丹参饮组大鼠的LVEF降低(P<0.05);与模型组比较,卡托普利组和低、中、高剂量加味丹参饮组大鼠LVEF升高(P<0.05)。与空白对照组比较,模型组大鼠HR、SBP、DBP、CO、LVSP和±dp/dtmax降低(P<0.05),LVEDP升高(P<0.05);与模型组比较,卡托普利组和低、中、高剂量加味丹参饮组大鼠SBP、DBP、CO、LVSP和±dp/dtmax升高(P<0.05),HR和LVEDP降低(P<0.05);与低剂量加味丹参饮组比较,卡托普利组和中、高剂量加味丹参饮组大鼠CO和±dp/dtmax升高(P<0.05),LVEDP降低(P<0.05)。与空白对照组比较,其他各组大鼠血清IL-6和TNF-α水平均有升高(P<0.05);与模型组比较,卡托普利组和低、中、高剂量加味丹参饮组大鼠血清中IL-6和TNF-α水平均明显降低(P<0.05);与低剂量加味丹参饮组比较,卡托普利组和中、高剂量加味丹参饮组大鼠血清中IL-6和TNF-α水平均明显降低(P<0.05)。与空白对照组比较,其他各组大鼠心脏和肺脏指数均明显增高(P<0.05);与模型组比较,卡托普利组和低、中、高剂量加味丹参饮组大鼠的心脏和肺脏指数均明显降低(P<0.05)。结论:加味丹参饮可改善心力衰竭大鼠的心脏功能并在一定程度上抑制血清炎性因子IL-6和TNF-α表达。在一定剂量范围内,中剂量加味丹参饮可使慢性心力衰竭大鼠心脏功能和血清炎性因子获得最大受益。
Objective:To investigate the effects of Jiawei Danshen Yin on the cardiac function and serum inflammatory factors interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in the rats with chronic heart failure,and to elucidate the mechanism of Jiawei Danshen Yin in the treatment of chronic heart failure.Methods:The SD rats were randomly divided into blank control group,heart failure model group,captopril group,and Low,medium,and high doses of Jiawei Danshen Yin groups.The rat models of chronic heart failure were prepared by intraperitoneal injection of adriamycin solution for 4 weeks.The left ventricular ejection fraction(LVEF)of the rats was measured by echocardiography.The heart rate(HR),cardiac output(CO),systolic blood pressure(SBP),carotid artery diastolic pressure(DBP),left ventricular end diastolic pressure(LVEDP),left ventricular systolic pressure(LVSP),left ventricular pressure change maximum increase/decrease rate(±dp/dtmax)and other related hemodynamic parameters were measured by ventilator in each group to assess the rat heart function.The levels of inflammatory cytokines IL-6 and TNF-αwere detected by enzyme-linked immunosorbent assay(ELISA).Results:Compared with blank control group,the LVEF of the rats in model group,captopril groups and low,medium,and high doses of Jiawei Danshen Yin groups were decreased(P<0.05).Compared with model group,the LVEF of the rats in captopril group and low,medium,and high doses of Jiawei Danshen Yin groups were increased(P<0.05).The HR,SBP,DBP,CO,LVSP,and ±dp/dtmaxof the rats in model group were lower than those in blank control group(P<0.05),while the LVEDP was increased(P<0.05).Compared with model group,the SBP,DBP,CO,LVSP and±dp/dtmax of the rats in captopril group and low,medium,and high doses of Jiawei Danshen Yin groups were increased(P<0.05),however the HR and LVEDP were decreased(P<0.05).Compared with low dose of Jiawei Danshen Yin group,the CO and ±dp/dtmaxof the rats in captopril group and medium and high doses of Jiawei Danshen Yin groups were increased(P<0.05)and the LVEDP were decreased(P<0.05).Compared with blank control group,the levels of serum IL-6 and TNF-αof the rats in the other groups were increased(P<0.05).The levels of serum IL-6 and TNF-αof the rats in captopril group and low,medium,and high doses of Jiawei Danshen Yin groups were lower than those in model group(P<0.05).Compared with low dose of Jiawei Danshen Yin group,the levels of serum IL-6 and TNF-αof the rats in captopril group and medium and high doses of Jiawei Danshen Yin groups were decreased(P<0.05).Compared with blank control group,the indexes of heart and lung in the other groups were all increased(P<0.05);compared with model group,the heart and lung indexes of the rats in captopril group and low,medium,and high doses of Jiawei Danshen Yin groups were decreased(P<0.05).Conclusion:Jiawei Danshen Yin can improve the heart function of the rats with heart failure and inhibit the expressions of serum inflammatory cytokines IL-6 and TNF-αto some extent.In the common dose range,Jiawei Danshen Yin can maximize the benefit of cardiac function and the serum inflammatory factors in the rats with chronic heart failure.
Objective:To investigate the effects of Jiawei Danshen Yin on the cardiac function and serum inflammatory factors interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in the rats with chronic heart failure,and to elucidate the mechanism of Jiawei Danshen Yin in the treatment of chronic heart failure.Methods:The SD rats were randomly divided into blank control group,heart failure model group,captopril group,and Low,medium,and high doses of Jiawei Danshen Yin groups.The rat models of chronic heart failure were prepared by intraperitoneal injection of adriamycin solution for 4 weeks.The left ventricular ejection fraction(LVEF)of the rats was measured by echocardiography.The heart rate(HR),cardiac output(CO),systolic blood pressure(SBP),carotid artery diastolic pressure(DBP),left ventricular end diastolic pressure(LVEDP),left ventricular systolic pressure(LVSP),left ventricular pressure change maximum increase/decrease rate(±dp/dtmax)and other related hemodynamic parameters were measured by ventilator in each group to assess the rat heart function.The levels of inflammatory cytokines IL-6 and TNF-αwere detected by enzyme-linked immunosorbent assay(ELISA).Results:Compared with blank control group,the LVEF of the rats in model group,captopril groups and low,medium,and high doses of Jiawei Danshen Yin groups were decreased(P<0.05).Compared with model group,the LVEF of the rats in captopril group and low,medium,and high doses of Jiawei Danshen Yin groups were increased(P<0.05).The HR,SBP,DBP,CO,LVSP,and ±dp/dtmaxof the rats in model group were lower than those in blank control group(P<0.05),while the LVEDP was increased(P<0.05).Compared with model group,the SBP,DBP,CO,LVSP and±dp/dtmax of the rats in captopril group and low,medium,and high doses of Jiawei Danshen Yin groups were increased(P<0.05),however the HR and LVEDP were decreased(P<0.05).Compared with low dose of Jiawei Danshen Yin group,the CO and ±dp/dtmaxof the rats in captopril group and medium and high doses of Jiawei Danshen Yin groups were increased(P<0.05)and the LVEDP were decreased(P<0.05).Compared with blank control group,the levels of serum IL-6 and TNF-αof the rats in the other groups were increased(P<0.05).The levels of serum IL-6 and TNF-αof the rats in captopril group and low,medium,and high doses of Jiawei Danshen Yin groups were lower than those in model group(P<0.05).Compared with low dose of Jiawei Danshen Yin group,the levels of serum IL-6 and TNF-αof the rats in captopril group and medium and high doses of Jiawei Danshen Yin groups were decreased(P<0.05).Compared with blank control group,the indexes of heart and lung in the other groups were all increased(P<0.05);compared with model group,the heart and lung indexes of the rats in captopril group and low,medium,and high doses of Jiawei Danshen Yin groups were decreased(P<0.05).Conclusion:Jiawei Danshen Yin can improve the heart function of the rats with heart failure and inhibit the expressions of serum inflammatory cytokines IL-6 and TNF-αto some extent.In the common dose range,Jiawei Danshen Yin can maximize the benefit of cardiac function and the serum inflammatory factors in the rats with chronic heart failure.
引文
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[11]陈白玉,李熙芹,陈晓利.肿瘤坏死因子-α、白细胞介素-1β、-6水平与充血性心力衰竭关系的临床研究[J].临床内科杂志,2006,23(3):184-185.
[12]KANDA T, TAKAHASHIT. Interleukin-6 and cardiovascular diseases[J].Jpn Heart J,2004,45(2):183-193.
[13] LEVINE B,KALMAN J, MAYER L,et al.Elevated circulating levels of tumor necrosis factor-alpha in severe chronic heart failure[J].N Engl J Med,1990,323(4):236-241.
[14] MANN D L,YOUNG J B.Basic mechanisms in congestive heart failure. Recognizing the role of proinflammatory cytokines[J].Chest,1994,105(3):897-904.
[15]NURAL-GUVENER H,ZAKHAROVA L,FEEHERY L,et al. Anti-fibrotic effects of classⅠHDAC inhibitor,mocetinostat is associated with IL-6/Stat 3 signaling in ischemic heart failure[J].Int J Mol Sci,2015,16(5):11482-11499.
[16]LOMMI J, PUIKKITK, KOSKINENP, etal.Haemodynamic,neuroendoerine and metabolic correlates of circulating cytokine concentrations in congestive heart failure[J].Eur Heart J,1997,18(10):1620-1625.
[17]王佳涛.慢性心力衰竭并贫血患者铁调节素、血清转铁蛋白受体肿瘤坏死因子-α、白介素-6的水平及意义[J].贵州医药,2016,40(5):480-481.
[18]唐利萍,何一婷,张斌霞.养心2号方对慢性心力衰竭模型大鼠血清炎性细胞因子的影响[J].中医学报,2017,32(11):2158-2161.
[19]张海涛,杜雨,曹芳芳,等.低心排血量综合征中国专家共识[J].解放军医学杂志,2017,42(11):933-944.
[20]孙冠军,王军,倪子琴.卡托普利联合美托洛尔治疗慢性心力衰竭50例疗效观察[J].医学理论与实践,2009,22(12):1440-1441.
[21]陈茂,范忠才,饶莉,等.心脏重量指数评价左心功能不全价值的研究[J].四川医学,2005,26(5):483-484.
[2]李凌华,左英,汪君,等.芪苈强心胶囊治疗慢性心力衰竭的疗效及对脑钠素和血清炎性因子的影响[J].陕西中医,2015,36(7):824-825.
[3]彭菂,蔡红靖.加味丹参饮治疗冠心病心绞痛心血瘀阻证的临床观察[J].光明中医,2018,33(1):7-9.
[4]陈聪,戴玉微,谭开云,等.加味丹参饮不同组方抗心肌缺血再灌注损伤的作用研究[J].湖南中医杂志,2016,32(6):164-166.
[5]金香兰.加味丹参饮联合西药治疗冠心病心绞痛心血瘀阻证35例疗效分析[J].中国实用医药,2016,11(25):181-182.
[6]成忠煌,胡雪峰,彭敏,等.阿霉素诱导大鼠慢性心力衰竭模型给药剂量和频率的优化[J].湖北中医杂志,2011,33(4):9-11.
[7]徐创业,蔺嫦燕.大动物心衰模型研究进展[J].北京生物医学工程,2013,32(5):536-540.
[8]曾瑾,崔凤娟,王海珍,等.阿霉素诱导和腹主动脉缩窄术复制大鼠慢性心力衰竭模型的比较[J].皖南医学院学报,2014,33(3):189-192.
[9]李玉玲,杨建业,唐俊明,等.阿霉素诱导大鼠心衰模型的不同方案的比较[J].中国比较医学杂志,2006,16(2):93-96,127.
[10]王靓,黄金玲,施慧,等.对慢性心力衰竭实验动物模型制作方法的研究进展[J].当代医药论丛,2014,12(10):291-293.
[11]陈白玉,李熙芹,陈晓利.肿瘤坏死因子-α、白细胞介素-1β、-6水平与充血性心力衰竭关系的临床研究[J].临床内科杂志,2006,23(3):184-185.
[12]KANDA T, TAKAHASHIT. Interleukin-6 and cardiovascular diseases[J].Jpn Heart J,2004,45(2):183-193.
[13] LEVINE B,KALMAN J, MAYER L,et al.Elevated circulating levels of tumor necrosis factor-alpha in severe chronic heart failure[J].N Engl J Med,1990,323(4):236-241.
[14] MANN D L,YOUNG J B.Basic mechanisms in congestive heart failure. Recognizing the role of proinflammatory cytokines[J].Chest,1994,105(3):897-904.
[15]NURAL-GUVENER H,ZAKHAROVA L,FEEHERY L,et al. Anti-fibrotic effects of classⅠHDAC inhibitor,mocetinostat is associated with IL-6/Stat 3 signaling in ischemic heart failure[J].Int J Mol Sci,2015,16(5):11482-11499.
[16]LOMMI J, PUIKKITK, KOSKINENP, etal.Haemodynamic,neuroendoerine and metabolic correlates of circulating cytokine concentrations in congestive heart failure[J].Eur Heart J,1997,18(10):1620-1625.
[17]王佳涛.慢性心力衰竭并贫血患者铁调节素、血清转铁蛋白受体肿瘤坏死因子-α、白介素-6的水平及意义[J].贵州医药,2016,40(5):480-481.
[18]唐利萍,何一婷,张斌霞.养心2号方对慢性心力衰竭模型大鼠血清炎性细胞因子的影响[J].中医学报,2017,32(11):2158-2161.
[19]张海涛,杜雨,曹芳芳,等.低心排血量综合征中国专家共识[J].解放军医学杂志,2017,42(11):933-944.
[20]孙冠军,王军,倪子琴.卡托普利联合美托洛尔治疗慢性心力衰竭50例疗效观察[J].医学理论与实践,2009,22(12):1440-1441.
[21]陈茂,范忠才,饶莉,等.心脏重量指数评价左心功能不全价值的研究[J].四川医学,2005,26(5):483-484.