次乌头碱、甘草苷及甘草次酸配伍对慢性心力衰竭大鼠的心肾保护作用研究

Protective Effects of Hypaconitine Combined with Glycyrrhetinic Acid and Glycyrrhizin on Heart and Kidney in Rats with Chronic Heart Failure

目的研究附子、甘草三种有效成分次乌头碱、甘草次酸、甘草苷配伍对慢性心力衰竭大鼠的心肾保护作用。方法应用主动脉弓缩窄术(TAC)建立慢性心力衰竭模型,将大鼠随机分为假手术组、模型组、阳性对照组(1mg/kg,地高辛组)、次乌头碱组(2.07mg/kg)、次乌头碱(2.07mg/kg)+甘草苷(20mg/kg)+甘草次酸(25mg/kg)配伍组(三药合用组),每组8只,各治疗组连续灌胃给药1周。干预结束6h后检测各组大鼠的超声心动图指标室间隔的厚度(IVSd)、左室后壁厚度(LVPWd)、左心室质量(LVMass)、左室短轴缩短率(FS)、左室射血分数(EF);腹主动脉取血后,取心、肾称重。酶联免疫法检测血浆中血管紧张素Ⅱ(AngⅡ)的含量变化;全自动生化检测仪检测血清BUN、SCr含量变化;HE染色评估心脏病理损伤情况;HE染色和Masson染色评估肾小球肾小管损伤情况以及肾间质纤维化程度。结果与模型组比较,三药合用组超声心动图指标IVSd、LVPWd、LVMass、FS、EF降低(P<0.01,P<0.05),BUN、SCr、AngⅡ浓度以及单侧肾比重降低(P<0.01,P<0.05),心、肾组织的病理损伤有明显改善。与次乌头碱组比较,三药合用组FS、EF、BUN、SCr、AngⅡ浓度降低(P<0.05),心、肾组织的病理损伤有改善。结论慢性心力衰竭可导致肾脏损伤,次乌头碱、甘草次酸、甘草苷配伍对慢性心力衰竭引起的左心室肥大、心功能障碍以及肾功能损伤有拮抗作用,三药合用的保护作用显著强于次乌头碱。

Objective To investigate the protective effects on heart and kidney of the combination of hypaconitine,glycyrrhetinic acid and glycyrrhizin which are the active ingredients of Aconitum carmichaelii and Glycyrrhiza uralensis Fisch.On chronic heart failure rats.Methods Chronic heart failure model was established by aortic arch narrowing（TAC）.The rats were randomly divided into five groups（n=8）,including sham-operated group,model group,positive control group（1 mg/kg）,hypaconitine group（2.07 mg/kg）and the group of the combination of hypaconitine（2.07 mg/kg）,glycyrrhetinic acid（25 mg/kg）and glycyrrhizin（20 mg/kg）,each treatment group was intragastrically administered for one week.The echocardiographic parameters of rats in each group,such as IVSd,LVPWd LVMass,FS,and EF were detected at 6 hours after intervention.The heart and kidney were taken to weigh after removing the abdominal aortic blood.Enzyme linked immunosorbent assay was used to detect the content of plasma AngiotensinⅡ（AngⅡ）,using the automatic biochemical detection instrumentation to detect the chan-ges of BUN and SCr content in serum,Hematoxylin and eosin（HE）staining was used to evaluate the pathological changes of the heart,evaluating Glomerular and tubular damage as well as the degree of renal interstitial fibrosis through HE and Masson stain.Results Compared with the model group,three drug combined group could reduce the echocardiographic indexes IVSd,LVPWd,LVMass,FS,EF（P〈0.01,P〈0.05）,the concentration of BUN,SCr,AngⅡ and the proportion of unilateral kidney decreased（P〈0.01,P〈0.05）,the heart and kidney tissue pathological damage were significantly improved.Compared with the hypaconitine group,the three drug combined group could significantly reduce the FS,EF and BUN,SCr,AngⅡ concentration（P〈0.05）,the heart and kidney tissue pathological lesions were improved.Conclusions Chronic heart failure can lead to kidney damage.The combination of hypaconitine,glycyrrhetinic acid and glycyrrhizin has antagonistic effects on left ventricular hypertrophy,cardiac dysfunction and renal function impairment caused by chronic heart failure,the protective effects of the three drugs combination is significantly stronger than hypaconitine.