生脉注射液与参附注射液单用及联用干预慢性心力衰竭小鼠的比较研究

Comparative Study of Shengmai Injection and Shenfu Injection Alone and in Combination for Chronic Heart Failure Mice

目的比较生脉注射液、参附注射液及其联合用药治疗盐酸异丙肾上腺素(ISO)诱导慢性心力衰竭(CHF)的效果。方法用ISO诱导建立CHF小鼠模型,将造模后的小鼠随机分为模型组(n=12)、生脉组(n=11)、参附组(n=11)和生参组(n=11)。同时设10只小鼠为空白组。生脉组、参附组分给予与生脉注射液[1.04 mL/(kg·d)]、参附注射液[1.04 mL/(kg·d)],生参组同时给予生脉注射液和参附注射液,空白组和模型组给予生理盐水,连续干预14 d。旷场实验观察小鼠行为,测量小鼠体重、脏器重量及左心室射血分数(LVEF),ELISA检测血清脑钠肽(BNP)水平,HE染色后镜下观察心肌组织形态,免疫组化染色法检测心肌B淋巴细胞瘤-2(Bcl-2)和Bcl-2相关X蛋白(Bax)的表达。结果空白组心肌细胞排列整齐,细胞核大小、形态与结构正常,模型组心肌细胞排列紊乱,细胞核大小与形态不均匀,生脉组心肌细胞排列较为整齐,也较少见细胞间质均质粉染区域,参附组、生参组心肌细胞排列较紊乱,细胞核大小、形态不均匀。与空白组比较,模型组体重、后肢直立次数、跨越格子数、LVEF、Bcl-2表达及Bcl-2/Bax下降(P<0.05,P<0.01),心重/体重、肺重/体重、肝重/体重、血清BNP水平、Bax表达升高(P<0.01)。与模型组比较,参附组体重、跨越格子数、Bcl-2表达及Bcl-2/Bax升高,肺重/体重、肝重/体重、血清BNP水平降低(P<0.05,P<0.01);生脉组肺重/体重、肝重/体重、血清BNP水平降低,梳理毛发次数、后肢直立次数、LVEF、Bcl-2和Bax表达、Bcl-2/Bax增加(P<0.05,P<0.01);生参组肺重/体重、肝重/体重、血清BNP水平降低,梳理毛发次数、后肢直立次数、跨越格子数、LVEF、Bcl-2和Bax表达、Bcl-2/Bax增加(P<0.05)。与参附组比较,生脉组Bcl-2表达及Bcl-2/Bax升高(P<0.05),Bax表达下降(P<0.05)。结论生脉注射液治疗ISO诱导CHF小鼠时,能更好地保护心肌,其疗效优于参附注射液及联合用药。

Objective To compare the effect of Shengmai Injection,Shenfu Injection and their combination on isoprenaline hydrochloride(ISO)induced chronic heart failure(CHF)mice.Methods CHF mice model was established by ISO induction,the model mice were randomly divided into model group(n=12),Shengmai group(n=11),Shenfu group(n=11)and Shengshen group(n=11),another 10 mice were selected as blank group.Shengmai group and Shenfu group were given Shengmai Injection(1.04 mL·kg-1·d-1)and Shenfu Injection(1.04 mL·kg-1·d-1)respectively.Shengshen group were given Shengmai Injection and Shenfu Injection.The blank group and model group were given normal saline Injection.The intervention lasted for 14 days.The behavior of mice was observed by open field test.Body weight,organ weight and left ventricular ejection fraction(LVEF)were measured.The serum level of brain natriuretic peptide(BNP)was detected by ELISA.The morphology of myocardial tissue was observed under microscope after HE staining.The expressions of B-cell lymphoma-2(Bcl-2)and Bcl2-associated X protein(Bax)were detected by immunohistochemical staining.Results In the blank group,the myocardial cells arranged neatly,the size,shape and structure of cell nucleus were normal.The myocardial cells in model group arrange disorderly,the cell nucleus uneven in the aspect of size and shape.The myocardial cells in Shengmai group arranged neatly,and the homogenous powder staining area between cells was less common.The arrangement of myocardial cells in Shenfu group and Shengshen group were disordered,and the size and shape of nucleus were uneven.Compared with the blank group,body weight,number of hind limb upright,number of square lattice be walked,LVEF,expression of Bcl-2 and Bcl-2/Bax decreased(P<0.05,P<0.01),while the ratio of heart weight/bodyweight,lung weight/body weight and liver weight/body weight,level of BNP in serum and expression of Bax increased in model group(P<0.01).Compared with model group,body weight,number of square lattice be walked,expression of Bcl-2 and Bcl-2/Bax increased,while the ratio of lung weight/body weight,liver weight/body weight and the level of BNP in serum decreased in Shenfu group(P<0.05,P<0.01).The ratio of lung weight/body weight,liver weight/body weight,the level of BNP in serum decreased,while grooming times,hind limb upright times,LVEF,expression of Bcl-2 and Bax,Bcl-2/Bax increased in Shengmai group(P<0.05,P<0.01).The ratio of lung weight/body weight,liver weight/body weight,BNP level in serum decreased,while grooming times,hind limb upright times,number of square lattice be walked,LVEF,expression of Bcl-2 and Bax,Bcl-2/Bax increased in Shengshen group(P<0.05).Compared with Shenfu group,expression of Bcl-2 and Bcl-2/Bax increased(P<0.05),while expression of Bax decreased in Shengmai group(P<0.05).Conclusion Shengmai injection has better myocardium protection effect in treatment of ISO-induced CHF mice,and its efficacy is better than Shenfu injection and the combination of Shengmai injection and Shenfu Injection.