苓桂气化2号方对射血分数保留心力衰竭大鼠心脏结构和舒张功能的影响

The effect of Linggui Qihua No.2 on the cardiac structure and diastolic function in rats with HFpEF

目的观察苓桂气化2号方对射血分数保留心力衰竭(heart failure with preserved ejection fraction,HFpEF)大鼠心脏结构和舒张功能的影响。方法10只7周龄的威斯塔京都大鼠作为正常组,40只自发性高血压大鼠建立复合糖尿病、高血压、高血脂的HFpEF大鼠模型,造模期间死亡3只。造模成功后,所有造模成功的大鼠随机分为模型组(9只)、恩格列净组(10只)、低剂量组(9只)和高剂量组(9只)。正常组和模型组给予等量生理盐水,恩格列净组给予恩格列净1.8 mg/(kg·d),低、高剂量组分别给予苓桂气化2号方浸膏8.1 g/(kg·d)和16.2 g/(kg·d),持续4周。给药结束后,使用超声心动图测量每组大鼠的左室舒末内径(left ventricular end diastolic diameter,LVEDD)、左房内径(left atrial diameter,LAD)、右房内径(right atrial diameter,RAD)、室间隔厚度(interventricular septal thickness,IVST)、左室射血分数(left ventricular ejection fraction,LVEF)、等容舒张时间(isovolumic relaxation time,IVRT)、舒张早期二尖瓣血流速度(left ventricular early diastolic filling peak velocity,E)与二尖瓣环心肌运动速度(early diastolic lateral mitral annulus velocity,e′)的值。使用酶联免疫吸附法检测心钠素(atrial natriuretic peptide,ANP)和脑钠肽(B-type brain natriuretic peptide,BNP)水平。苏木精—伊红染色观察左房心肌组织病理变化,马松染色染色观察心肌组织纤维化。结果与正常组比较,模型组大鼠出现呼吸急促、食欲下降、易怒等情况,心脏超声检测显示LVEDD、LAD、RAD显著增大(P<0.01),IVST、E/e′、IVRT显著增加(P<0.01);血清ANP、BNP水平显著升高(P<0.01)。与模型组相比,各给药组大鼠精神佳、反应灵敏、纳食饮水相对较多,心脏超声相关参数显示LVEDD、LAD、RAD、IVST以及E/e′、IVRT均有明显改善(P<0.05);血清ANP、BNP水平均明显降低(P<0.05)。结论苓桂气化2号方可能通过减轻心肌肥厚及纤维化改善HFpEF大鼠的心脏重构和舒张功能障碍,是治疗HFpEF的潜在有效方剂。

Objective To observe the effect of Linggui Qihua No.2(LGQH2)on the cardiac structure and diastolic function in rats with heart failure with preserved ejection fraction(HFpEF)rats.Methods Ten 7-week-old WKY rats were used as the normal group,and 40 SHR rats were used to establish HFpEF model with composite diabetes,hypertension,and hyperlipidemia.Three rats were died at this stage.After successful modeling,all rats were randomly divided into the model group,the empagliflozin group,the low-and the high-dose decoction groups.The WKY and the model group received an equal dose of normal saline.The intervention groups were administered empagliflozin[1.8 mg/(kg•d)],low-dose[8.1 g/(kg•d)]and high-dose decoction[16.2 g/(kg•d)],respectively,for 4 weeks.At the end of the intervention,echocardiography was used to measure left ventricular end-diastolic internal diameter(LVEDD),left atrial internal diameter(LAD),right atrial internal diameter(RAD),interventricular septal thickness(IVST),and the ratios of left ventricular ejection fraction(LVEF),isovolumic diastolic time(IVRT),and the ratio of the early diastolic mitral blood flow rate(E)to mitral annular myocardial motion velocity(e′).The level of atrial and brain natriuretic peptide in serum were measured using enzyme-linked immunosorbent assay.Pathological changes in left atrial myocardial tissue were observed by HE staining,and myocardial tissue fibrosis was observed with Masson staining.Results Compared with the WKY group,The rats in the model group showed shortness of breath,decreased appetite and irritability.The LVEDD,LAD,RAD,IVST,E/e′,IVRT,as well as the level of ANP and BNP were significantly increased in the model group(P<0.01).Compared with the model group,the rats in each treatment group were in good spirits,responsive,and took more food and water.The LVEDD,LAD,RAD,IVST,E/e′and IVRT were improved significantly in the administration groups and the level of ANP and BNP were significantly decreased(P<0.05).Conclusion LGQH2 decoction may improve cardiac remodeling and diastolic dysfunction in HFpEF rats by attenuating myocardial hypertrophy and fibrosis,and become a valuable prescription for HFpEF.