基于均匀设计法探讨黄芪总皂苷-荷叶总生物碱防治高脂血症的剂量配比

Study on the Dose Ratio of Total Saponins of Astragalus Membranaceus-Total Alkaloids of Lotus Leaf to Prevent and Treat Hyperlipidemia Based on Uniform Design

目的:运用均匀设计法探讨黄芪总皂苷-荷叶总生物碱防治高脂血症的最佳剂量配比,探讨中药有效组分的配伍、配比规律。方法:将黄芪总皂苷、荷叶总生物碱2种有效组分按照均匀设计法中的实验方案进行配比,得到7种不同剂量的配比组,分别用于防治高脂饮食诱导的高脂血症模型大鼠,并以甘油三脂(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDLC)、谷草转氨酶(AST)、谷丙转氨酶(ALT)作为筛选指标,优选二者最佳剂量配比,并对筛选结果进行实验验证。结果:筛选实验表明:模型组大鼠血清中TG、TC、LDL-C、AST、ALT的含量或活性均明显高于正常组(P<0.05或P<0.01);肝组织出现脂肪变性。经二次多项式逐步回归分析,二者组合的最佳剂量配比是黄芪总皂苷34mg/kg+荷叶总生物碱80mg/kg。验证实验结果表明:黄芪总皂苷、荷叶总生物碱最佳剂量配比组能明显降低实验性高脂血症大鼠血清中TC、TG、LDL-C和肝组织中TC、TG含量的异常升高(P<0.01),并能改善肝脏脂肪变性。结论:应用均匀设计与药效学研究方法,可优化黄芪总皂苷与荷叶总生物碱防治高脂血症的最佳剂量配比。

Objective:To explore the optimal dose ratio of total saponins of astragalus membranaceus-total alkaloids of lotus leaf combined in the prevention and treatment of hyperlipidemia by uniform design method,and to explore the compatibility ratio rule of effective components of traditional Chinese medicine.Methods:Using uniform design method,seven doses of total saponins of astragalus membranaceus-total alkaloids of lotus leaf were used to prevent and treat hyperlipidemia model induced by high fat diet.Triglyceride(TG),cholesterol(TC),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),aspartate aminotransferase(AST)and alanine aminotransferase(ALT)were used for the screening-indexes,and the further experiments were taken to verify the results.Results:Screening experiment showed that the contents or activities of TG,TC,LDL-C,AST and ALT in serum of model group were significantly higher than the normal group(P<0.05or P<0.01).Steatosis was observed in the liver.By quadratic polynomial stepwise regression analysis,the optimal dosage ratio of total saponins of astragalus membranaceus-total alkaloids of lotus leaf was 34mg/kg+80mg/kg.The results showed that the optimal dose ratio of total saponins of astragalus membranaceus-total alkaloids of lotus leaf could significantly reduce the abnormal increase of TC,TG,LDL-C in serum and TC,TG in liver of hyperlipidemia rats(P<0.01),and improve hepatic steatosis.Conclusion:The optimal dose ratio of total saponins of astragalus membranaceus-total alkaloids of lotus leaf in the prevention and treatment of hyperlipidemia can be optimized by uniform design and pharmacodynamics study.