基于“以方测证”探讨异丙肾上腺素诱导慢性心衰小鼠模型的中医证型及证候本质

Chinese Medical Syndrome and Nature of Isoproterenol-Induced Chronic Heart Failure Mice Based on Syndrome Determination by Formulas

目的:采用异丙肾上腺素(ISO)诱导慢性心衰小鼠模型,选用气虚证的代表方黄芪注射液、血瘀证的代表方丹红注射液、气阴两虚证的代表方参麦注射液及阳虚证的代表方参附注射液进行干预,从“以方测证”角度探索该模型的证候属性。方法:通过腹腔注射ISO 7.5 mg/kg进行造模,造模成功后将其分为模型对照组、黄芪注射液9.0 mL/kg组、丹红注射液9.0 mL/kg组、参麦注射液9.0 mL/kg组、参附注射液9.0 mL/kg组和卡托普利16.5 mg/kg组,另设正常对照组。药物干预15 d后,对其进行心功能评价,测定血清NT-proBNP、TNF-α、IL-6含量,检测心、脾及肾组织病理,结合宏观表征探讨其中医证型。结果:与正常对照组比较,模型对照组LVEF、LVFS、LVPWd、LVPWs、IVSd、IVSs值显著降低(P<0.01),LVIDd、LVIDs、LVEDV、LVESV水平,血清NT-proBNP、TNF-α、IL-6含量显著升高(P<0.01);与模型对照组比较,参附组、卡托普利组LVIDd、LVIDs、LVEDV、LVESV水平,血清NT-proBNP、TNF-α、IL-6含量明显降低(P<0.05或P<0.01),LVEF、LVFS LVPWd值明显升高(P<0.05或P<0.01);参附组、卡托普利组在改善心、脾、肾病理形态学疗效优于其他注射液。结论:参附注射液对ISO诱导心衰小鼠模型的疗效显著且优于黄芪、丹红、参麦注射液,推测该模型的证候属性可能为心阳虚证。

Objective:The mouse model of chronic heart failure(CHF)was induced by isoproterenol(ISO).Huangqi(黄芪)Injection,a representative formula for qi(气)deficiency syndrome,Danhong(丹红)Injection,a representative formula for blood stasis syndrome,Shenmai(参麦)Injection,a representative formula for syndrome of deficiency of both qi and yin(阴),and Shenfu(参附)Injection,a representative formula for yang(阳)deficiency syndrome were administrated to explore the properties of this model from the perspective of syndrome determination by formulas.Methods:The model was established by intraperitoneal injection of ISO(7.5 mg/kg).After successful modeling,mice were divided into the model group,Huangqi injection group(9.0 mL/kg),Danhong injection group(9.0 mL/kg),Shenmai injection group(9.0 mL/kg),Shenfu injection group(9.0 mL/kg),and captopril group(16.5 mg/kg),and a normal control group.After 15 d of drug intervention,cardiac function,NT-proBNP,TNF-α,IL-6,heart,spleen,and kidney histopathological tests were performed to explore their Chinese medical syndrome in conjunction with macroscopic phenotypes.Results:Compared with the normal control group,the LVEF,LVFS,LVPWd,LVPWs,IVSd,and IVSs values were significantly decreased in the model group(P<0.01),and LVIDd,LVIDs,LVEDV,LVESV,NT-proBNP,TNF-α,and IL-6 were significantly increased(P<0.01).Compared with the model group,the values of LVIDd,LVIDs,LVEDV,LVESV,NT-proBNP,TNF-α,and IL-6 were significantly decreased in the Shenfu group and captopril group(P<0.05 or P<0.01),while the values of LVEF,LVFS,and LVPWd were significantly increased(P<0.05 or P<0.01).The efficacy of Shenfu and captopril groups in improving the pathomorphology of the heart,spleen,and kidney was superior to other injections.Conclusion:The efficacy of Shenfu Injection in the mouse model with ISO-induced CHF was significant and superior to that of Huangqi,Danhong,and Shenmai injections,and it was speculated that the syndrome attribute of this model may be heart Yang deficiency syndrome.