黄芪甲苷对糖尿病大鼠心肌肥厚的作用及机制研究

Effects and mechanism of astragaloside-IV on diabetic ardiomyopathy

目的 探讨黄芪甲苷（astragaloside-IV,ASG-IV）对糖尿病心肌病变（Diabetic cardiomyopathy,DCM）模型大鼠心肌的保护作用,并进一步探索ASG-IV对DCM保护作用机理。方法 采用40只Sprague-Dawley（SD）大鼠,尾静脉注射链脲佐菌素（streptozotocin,STZ）45 mg/kg,3d,诱发DM,另10只注射等量枸橼酸缓冲液作为对照组。72h后,大鼠空腹血糖≥16.7 mmol/L为DM大鼠造模成功。高糖、高脂饮食12w后,造成DCM模型。随机分为5组,包括对照组、DCM损伤组、ASG-IV低剂量（10mg/kg）、ASG-IV中剂量（30mg/kg）及ASG-IV高剂量（60mg/kg）组。给药4w后,分别采用全自动生化分析仪测定血清肌酸激酶（phosphokinase isoenzyme,CK-MB）和乳酸脱氢酶（lactic dehydrogenase,LDH）含量,取心脏计算心重指数（heart weight index=heart weight/body weight,HWI=HW/BW）和左心指数（left ventricle weight index=left ventricle weight/body weight,LVWI=LVW/BW）制备心肌匀浆ELISA法测定游离脂肪酸（free fatty acid,FFA）的浓度,Na~＋-K~＋-ATP酶和Ca^（2＋）-ATP酶活性。结果 与对照组相比,DCM模型组大鼠血糖显著增高,具有显著性差异（P〈0.05）,LDH及CK-MB水平均明显升高,HWI、LVWI也升高,具有显著性差异（P〈0.05）。给予不同剂量ASG-IV后,ASG-IV能够降低DCM大鼠的HWI、LVWI、CK-MB及LDH水平,对DCM起抑制增值肥厚的作用,与DCM模型组相比具有显著性差异（P〈0.05）。另外,ASG-IV还能降低FFA浓度,保护Ca^（2＋）-ATP酶和Na~＋-K~＋-ATP酶活性,与DCM模型组相比具有显著性差异（P〈0.05）。结论 ASG-IV可能是通过降低FFA浓度,保护Ca^（2＋）-ATP酶和Na~＋-K~＋-ATP酶活性,改善心肌能量代谢作用,发挥对DCM心肌的保护作用。

Objective To study the therapeutic effects and mechanisms of Astragaloside-IV （ASG-IV） on diabetic cardiomyopathy （DCM） in the rat diabetic model. Methods Forty SD （Sprague-Dawley） healthy rats were used. The diabetic retinopathy rats model were induced by STZ, 45 mg/kg, 3d. Another 10 were injected the same amount of citrate buffer as a control group. Fasting blood glucose was measured with SureStep Plus detector 72 h later. The blood glucose of the diabetes model was 〉16.7 mmol/L. And 12 weeks later, DCM rats were divided into 4 groups randomly in the experiment, includes DCM, ASG-IV-L （10 mg/kg）, ASG-IV-M （30 mg/kg）, ASG-IV-H （60 mg/kg）groups. After give dugs 4 weeks, the phosphokinase isoenzyme （CK-MB） and LDH level were tested, the cardiac hypertrophy was evaluated by HW/BW and LVW/BW. Activity of Na＋-K＋-ATPase and Ca2＋-ATPase were determined in left ventricular tissues by ATPase ELISA Assay Kit. The content of FFA was measured and myocardial pathological examination was performed. Results Compared with the control group, blood and urine glucose were higher than experimental animal in diabetic model group, were significantly increased （P〈0.05）. LDH and Phosphokinase isoenzyme （CK-MB） level weresignificantly increased, the HWI and LVWI ratio were enhanced in DCM group （P〈0.05）. ASG-IV could reduce the ratio of HWI and LVWI, decrease the level of CK-MB and LDH, improve the pathomorphological changing of DCM rat model （P〈0.05）. Moreover, compared with DCM group, ASG- IV could restore the Na＋-K＋-ATPase and Ca2＋-ATPase activity, reduced the content of FFA （P〈0.05）. Conclusion ASG-IV plays therapeutic effect on diabetic cardiomyopathy might via restore the Na＋-K＋-ATPase and Ca2＋-ATPase activity, reduce the content of FFA, protect the myocardial energy metabolism in DCM.