扶正化瘀方抗肝纤维化主要成分的配伍研究

Study on the Compatibility of the Main Components of Fuzheng Huayu Formula Against Hepatic Fibrosis

目的基于均匀设计法探索扶正化瘀方(Fuzheng Huayu,FZHY)有效成分组合及配伍效应。方法以扶正化瘀方提取物中含量最高的丹参化合物成分F-01及主要入血桃仁活性成分F-02及五味子成分F-03为研究对象,运用均匀设计法,以肝组织羟脯氨酸(hydroxyproline,Hyp)含量和天狼猩红(Sirius red,SR)染色胶原半定量为筛选指标,采用四氯化碳(carbon tetrachloride,CCl_(4))和胆管结扎(bile duct ligation,BDL)诱导大鼠肝纤维化模型,经回归分析获得"最佳配方",并进行再验证。结果(1)均匀设计方案中的JY5组合可显著降低CCl_(4)和BDL诱导的肝纤维化大鼠血清丙氨酸氨基转移酶(alanine aminotransferase,ALT)和天冬酸氨基转移酶(aspartate aminotransferase,AST)活性,提高血清白蛋白(albumin,ALB)含量,降低肝组织羟脯氨酸(hydroxyproline,Hyp)含量及胶原面积半定量;其回归方程则提示配方P(F-01(32 mg·kg^(-1))+F-02(0.5 mg·kg^(-1))+F-03(0.5 mg·kg^(-1)))是三者降低CCl_(4)肝纤维化大鼠肝组织Hyp含量和BDL肝纤维化大鼠肝组织胶原沉积从而发挥抗肝纤维化作用的最佳配比。(2)验证实验表明配方P对CCl_(4)和BDL肝纤维化大鼠血清ALT、AST、ALB及肝组织Hyp含量及胶原面积半定量并无显著改善作用,而JY5的抗肝纤维化作用在CCl_(4)和BDL肝纤维化大鼠实验中均得到再证实。结论(1)F-01(16 mg·kg^(-1))+F-02(0.5 mg·kg^(-1))+F-03(2mg·kg^(-1))组合可显著改善CCl_(4)和BDL大鼠肝纤维化,疗效与FZHY原方相当。(2)均匀设计对量效关系呈非线性的中药复方效应成分的研究可能有其一定局限性。

Objective To explore the effective ingredient combination and compatibility meaning of Fuzheng Huayu Formula(FZHY)based on the uniform design method.Methods The content of hydroxyproline(Hyp)in liver tissue was used as the screening index.The compatibility ratio of F-01,F-02 and F-03 was explored based on the uniformly design and the results were verified through the CCl_(4)-induced rat liver fibrosis model.Results(1)JY5 group(F-01(16 mg·kg^(-1))+F-02(0.5 mg·kg^(-1))+F-03(2 mg·kg^(-1)))can significantly reduce the activity of serum ALT and AST,increase serum ALB content,reduce the content of Hyp in liver tissue and semi-quantitative of collagen area,thereby improving liver fibrosis induced by CCl_(4)in rats.The regression equation suggests the formula P(F-01(32 mg·kg^(-1))+F-02(0.5 mg·kg^(-1))+F-03(0.5 mg·kg^(-1)))was the best ratio of three components.(2)Validation experiments showed that JY5 had a good effect of anti-hepatic fibrosis,while formula P had no effects on liver fibrosis.Conclusion(1)The combination of F-01(16 mg·kg^(-1))+F-02(0.5 mg·kg^(-1))+F-03(2 mg·kg^(-1))can significantly improve CCl_(4)-induced liver fibrosis in rats,and the effect is equivalent to FZHY.(2)Uniform design may have limitations in the study of the effect components of traditional Chinese medicine compounds with a nonlinear dose-effect relationship.