机构地区:[1]北京市宣武中医医院心内科,100050 [2]北京中医药大学东直门医院中医内科实验室 [3]首都医科大学附属北京中医医院心血管科
出 处:《环球中医药》2023年第5期824-830,共7页Global Traditional Chinese Medicine
摘 要:目的观察中药复方调脉饮对射血分数保留心衰大鼠心肌纤维化的影响及其机制。方法采用缩窄大鼠腹主动脉制备心力衰竭模型,随机分为假手术组、模型组、西药组(依那普利干预)、调脉饮组,从术后第2天开始给药,干预12周。采用左心室插管检测心脏收缩和舒张功能;Masson和免疫组化测定心肌组织胶原含量;放射免疫法检测心肌和血清中血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)含量;蛋白免疫印迹法检测AngⅡ受体1(AngⅡtype 1 receptor,AGTR1)、α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)、转化生长因子β(transforming growth factor-β,TGF-β)、纤连蛋白(fibronectin,FN)以及Smad7蛋白。结果与假手术组比,模型组的左心室收缩压(left ventricular systolic pressure,LVSP)和左心室开始收缩至左室内压最大变化速率(dp/dtmax)间隔时间(t-dp/dtmax)无明显变化,而左心室平均压显著上升(P<0.01),左心室内压最大上升速率(+dp/dtmax)明显减少(P<0.05),左心室终末舒张压、左心室内压最大下降速率(-dp/dtmax)和左心室压力下降时间常数均明显升高(P<0.05,P<0.01)。调脉饮组和西药组对左心室收缩功能无明显影响,对左心室舒张指标左心室舒张压、左心室终末舒张压和-dp/dtmax的均值都有降低但无统计学差异。模型组心肌胶原容积分数明显高于假手术组(P<0.01)。调脉饮组和西药组心肌胶原容积分数均明显降低(P<0.01)。与假手术组比较,模型组心肌组织及血中的AngⅡ明显增加(P<0.05),心肌组织中TGF-β明显升高而Smad7蛋白明显降低(P<0.05)。与模型组比较,调脉饮和西药可显著降低血中AngⅡ的含量(P<0.05),同时明显降低心肌组织TGF-β含量,升高Smad7蛋白水平(P<0.05)。结论调脉饮有一定改善舒张功能的趋势,明显改善射血分数保留心衰大鼠的心肌纤维化,其机制可能与降低血中AngⅡ的含量、降低心肌组织TGF-β、升高Smad7蛋白表达含量有关。Objective To observe the effect and mechanism of Chinese medicine compound Tiaomaiyin on myocardial fibrosis in rats with preserved ejection fraction heart failure.Methods A heart failure model was established by constricting rat abdominal aorta and rats were randomly divided into sham operation group,model group,western medicine(enalapril)group and Tiaomaiyin group.The drugs were administered from the 2nd postoperative day and intervened for 12 weeks.Systolic and diastolic functions were detected by left ventricular intubation.Masson and immunohistochemistry were used to determine the collagen content of myocardial tissue.The concentrations of angiotensinⅡ(AngⅡ)in myocardium and serum were determined by radioimmunoassay.AngⅡreceptor 1(AGTR1),α-smooth muscle agonist protein(α-SMA),transforming growth factorβ(TGF-β),fibronectin(FN)and Smad7 proteins were detected by Western blot.Results Compared with sham operation group,there were no significant changes in the left ventricular systolic pressure(LVSP)and the interval time from left ventricular contraction to+dp/dtmax(T-dp/dtmax)in the model group,while the mean left ventricular pressure(LVAP)increased significantly(P<0.01)and+dp/dtmax decreased significantly(P<0.05).Left ventricular end diastolic pressure(LVEDP),maximum rate of pressure drop in left ventricle(-dp/dtmax)and time constant of pressure drop in left ventricle(T)went up evidently(P<0.05,or P<0.01).There was no significant effect on Tiaomaiyin and western medicine,and the mean values of LVDP,LVEDP and-dp/dtmax were reduced but not statistically different.Myocardial collagen volume fraction(CVF)in model group was obviously higher than that in sham group(P<0.01),and Tiaomaiyin and western medicine significantly decreased CVF(P<0.01).Compared with sham operation group,AngⅡin myocardium and blood was distinctly increased(P<0.05),TGF-βin myocardium was significantly increased and Smad7 protein was significantly decreased(P<0.05)in model group.Compared with model group,Tiaomaiyin and western medic
关 键 词:调脉饮 心力衰竭 心肌纤维化 血管紧张素Ⅱ 转化生长因子-β信号通路
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