补肾活血汤对慢性心力衰竭大鼠心功能及免疫炎症反应的影响
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摘要
目的观察补肾活血汤对慢性心力衰竭大鼠心功能以及血清白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、血清正五聚蛋白3(PTX3)水平的影响,并探讨其治疗心力衰竭的潜在作用机制。方法通过腹腔注射阿霉素复制心力衰竭模型,将造模成功后的Wistar大鼠随机分为补肾活血汤高剂量组、补肾活血汤中剂量组、补肾活血汤低剂量组、卡托普利组、模型组,并设立空白组,分别给药4周,空白组灌胃生理盐水4周。利用心脏彩超测量左心室射血分数(LVEF)、左室短轴缩短率(LVFS)。用酶联免疫法(ELISA)检测心力衰竭大鼠血清中IL-6、TNF-α、PTX3及脑钠肽(BNP)水平。结果与空白组相比,模型组LVEF、LVFS水平明显降低(P <0.01);与模型组相比,补肾活血汤中剂量组和高剂量组LVEF、LVFS水平明显升高(P <0.05或P <0.01),IL-6、TNF-α、PTX3及BNP水平明显下降(P <0.01)。结论补肾活血汤能调控心力衰竭时大鼠细胞因子及神经内分泌水平,这可能是补肾活血汤减少心力衰竭炎症细胞因子分泌、改善神经内分泌紊乱、干预心室重构、抑制心力衰竭的生化机制之一。
Objective To observe the effect of Bushen Huoxue decoction(BHD)on cardiac function and the levels of serum interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)and serum pentameric protein 3(PTX3)in rats with chronic heart failure(CHF),and to explore its potential mechanism.Methods The rat model of CHF was established by intraperitoneal injection of doxorubicin.After successful modeling,Wistar rats were randomly divided into BHD high-dose group,BHD medium-dose group,BHD low-dose group,captopril group and model group,and a blank group was set up.After 4 weeks of administration,the rats in blank group were orally administered with normal saline for 4 weeks.The left ventricle ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)were calculated by color Doppler echocardiography to evaluate cardiac function.The levels of serum IL-6,TNF-α,PTX3 and brain natriuretic peptide(BNP)were detected by enzyme-linked immunosorbent assay(ELISA).Results Compared with the blank group,the levels of LVEF and LVFS in the model group were significantly lower(P <0.01).Compared with the model group,the levels of LVEF and LVFS in BHD medium-dose group and BHD high-dose group were significantly increased(P <0.05 or P <0.01),IL-6,TNF-α,PTX3 and BNP levels were significantly decreased(P <0.01).Conclusion BHD can regulate the levels of cytokines and neuroendocrine in rats with CHF.This may be one of the biochemical mechanisms of BHD to reduce the secretion of inflammatory cytokines,improve neuroendocrine disorders,interfere with ventricular remodeling,and inhibit heart failure.
Objective To observe the effect of Bushen Huoxue decoction(BHD)on cardiac function and the levels of serum interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)and serum pentameric protein 3(PTX3)in rats with chronic heart failure(CHF),and to explore its potential mechanism.Methods The rat model of CHF was established by intraperitoneal injection of doxorubicin.After successful modeling,Wistar rats were randomly divided into BHD high-dose group,BHD medium-dose group,BHD low-dose group,captopril group and model group,and a blank group was set up.After 4 weeks of administration,the rats in blank group were orally administered with normal saline for 4 weeks.The left ventricle ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)were calculated by color Doppler echocardiography to evaluate cardiac function.The levels of serum IL-6,TNF-α,PTX3 and brain natriuretic peptide(BNP)were detected by enzyme-linked immunosorbent assay(ELISA).Results Compared with the blank group,the levels of LVEF and LVFS in the model group were significantly lower(P <0.01).Compared with the model group,the levels of LVEF and LVFS in BHD medium-dose group and BHD high-dose group were significantly increased(P <0.05 or P <0.01),IL-6,TNF-α,PTX3 and BNP levels were significantly decreased(P <0.01).Conclusion BHD can regulate the levels of cytokines and neuroendocrine in rats with CHF.This may be one of the biochemical mechanisms of BHD to reduce the secretion of inflammatory cytokines,improve neuroendocrine disorders,interfere with ventricular remodeling,and inhibit heart failure.
引文
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[12]BUYUKKAYA E,KARAKAS M F,KURT M,et al.The serum pentraxin-3 is elevated in patients with cardiac syndrome X[J].Turk Kardiyol Dern Ars,2013,41(4):290-295.
[13]高景顺,刘鹏.正五聚蛋白3检测在老年慢性心力衰竭中的诊疗价值[J].中国老年学杂志,2014,34(13):3742.
[14]李雨真,朱栋栋,李洁,等.补肾活血汤对慢性心力衰竭大鼠血清sFas、MMP2的影响[J].世界中西医结合杂志,2012,7(15):394-396.
[2]陈奇.中药药理研究方法学[M].北京:人民卫生出版社,1993:69-71.
[3]NEUMANN F J,MARX N,GAWAZ M,et al.Induction of cytokine expression in leukocytes by binding of thrombin-stimulated platelets[J].Circulation,1997,95(10):2387-2394.
[4]HAQUE R,KAN H,FINKEL M S.Effects of cytokines and nitric oxide on myocardial E-C coupling[J].Basic Research in Cardiology,1998,93(1):86-94.
[5]BIRKS E J,LATIF N,OWEN V,et al.Quantitative myocardial cytokine expression and activation of the apoptotic pathway in patients who require left ventricular assist devices[J].Circulation,2001,104:1233-1240.
[6]SIWIK D A,CHANG D L,COLUCCI W S.Interleukin-1beta and tumor necrosis factor-alpha decrease collagen synthesis and increase matrix metalloproteinase activity in cardiac fibroblasts in vitro[J].Circulation Research,2000,86(12):1259.
[7]SANO M,FUKUDA K,KODAMA H,et al.Interleukin-6 family of cytokines mediate angiotensinⅡ-induced cardiac hypertrophy in rodent cardiomyocytes[J].Journal of Biological Chemistry,2000,275(38):29717-29723.
[8]TORRE-AMIONE G,KAPADIA S,LEE J,et al.Expression and functional significance of tumor necrosis factor receptors in human myocardium[J].Circulation,1995,92(6):1487-1493.
[9]MICHAEL T,PHILIP W,HARTMUT K,et al.Chronic inflammatory cardiomyopathy of interferon-γoverexpressing transgenic mice is mediated by tumor necrosis factor-α[J].American Journal of Pathology,2012,180(1):73-81.
[10]崔修岭.短期小剂量米力农治疗扩张型心肌病顽固性心衰的应用效果观察[J].中国伤残医学,2016,24(3):102-103.
[11]BYRKJELAND R,NILSSON B B,WESTHEIM A S,et al.Inflammatory markers and disease severity in patients with chronic heart failure:limited effects of exercise training[J].Scandinavian Journal of Clinical&Laboratory Investigation,2011,71(7):598-605.
[12]BUYUKKAYA E,KARAKAS M F,KURT M,et al.The serum pentraxin-3 is elevated in patients with cardiac syndrome X[J].Turk Kardiyol Dern Ars,2013,41(4):290-295.
[13]高景顺,刘鹏.正五聚蛋白3检测在老年慢性心力衰竭中的诊疗价值[J].中国老年学杂志,2014,34(13):3742.
[14]李雨真,朱栋栋,李洁,等.补肾活血汤对慢性心力衰竭大鼠血清sFas、MMP2的影响[J].世界中西医结合杂志,2012,7(15):394-396.