基于主成分分析评价雷公藤配伍金钱草的相杀减毒作用

目的:考察雷公藤(LGT)配伍金钱草(JQC)的相杀减毒作用,优选二者的最佳配比,初步评价二者配伍后特征化学成分的贡献程度。方法:通过小鼠连续给药14 d的亚急性毒性试验并基于主成分分析优选LGT配伍JQC后相杀减毒作用的最佳配比,给药剂量以LGT提取物计均为60 mg·kg-1(相当于LGT生药约2 g·kg-1),给药体积均为20 m L·kg-1。基于常规小鼠急性毒性试验评价最佳配比的减毒效果,通过对配伍前后差异特征化学成分与总体减毒作用的灰色关联分析,评价化学成分对其相杀减毒作用的贡献大小。结果:与正常组比较,LGT单用组极显著升高了小鼠血清生化指标丙氨酸氨基转移酶(ALT),天门冬氨酸氨基转移酶(AST),肌酐(Cr)和尿素氮(BUN)水平,肝组织和肾组织中的脂质过氧化指标丙二醛(MDA)水平以及总体减毒作用得分Z值(P0.01)。与LGT单用组比较,LGT-JQC质量比为2∶1,1∶1,1∶2,1∶4的配伍组均能显著降低LGT引起的血清过高的ALT水平(P0.05,P0.01),质量比为4∶1,2∶1,1∶1,1∶2,1∶4配伍时均能显著降低LGT引起的过高的血清AST,Cr,BUN,肝MDA水平以及总体减毒作用得分Z值(P0.05,P0.01),质量比为4∶1,2∶1,1∶1配伍时均能显著降低LGT引起的肾过高的MDA水平(P0.05,P0.01)。LGT和JQC在各质量比(4∶1,1∶1,1∶2,1∶4)配伍时的总体减毒作用Z值均明显高于配比在2∶1时的Z值(P0.01)。LGT单独用药对小鼠的半数致死量(LD50)517 mg·kg-1,LGT-JQC(2∶1)配伍用药时的LD50升高至889 mg·kg-1,升高了72%。配伍前后12个差异特征化学成分与其总体减毒作用得分Z值的灰色关联系数最大的是雷公藤甲素(TP)。结论:LGT和JQC在质量比为4∶1~1∶4配伍时,对LGT所致亚急性肝毒和肾毒均具有配伍减毒作用,二者相杀减毒的最佳配比为2∶1;在2∶1配比时,急性毒性和亚急性毒性分别下降了72%和138.5%;TP是引起二者相杀减毒作用贡献最大的化学成分。

Evaluation on Mutual Detoxication of Compatibility of Tripterygii Radix et Rhizoma and Lysimachiae Herba Based on Principal Component Analysis

Objective: To observe effects on attenuated toxicity of Tripterygii Radix et Rhizoma(LGT) by compatibility with Lysimachiae Herba(JQC), screen out the best proportion between them and give preliminary evaluation of its chemical contribution. Method: The best proportion in the toxicity-attenuated effects of LGT by compatability with JQC was screened out by principal component analysis(PCA) in the subacute toxicity test of mice orally administrated for 14 consecutive days, then such effect at the best proportion was evaluated in the conventional acute toxicity test of mice, and finally its contribution of the chemical difference characteristic components to overall efficacy was assessed by the gray correlation analysis(GCA). Result: Compared with the normal group, LGT alone group significantly elevated serum biochemical markers, including alanine aminotransferase(ALT), aspartate aminotransferase(AST), creatinine(Cr) and urea nitrogen(BUN) levels, malondialdehyde(MDA) levels in the liver and kidney tissues, as well as the overall efficacy of Z value(P<0.01).Compared with LGT alone group, the combined groups of LGT and JQC significantly reduced LGT-induced excessively high levels of ALT when the mass ratio was 2:1, 1:1, 1:2 or 1:4(P<0.05, P<0.01), those of serum AST, Cr, BUN, liver MDA and Z value when the ratio was 4:1, 2:1, 1:1, 1:2 or 1:4(P<0.05, P<0.01), and those of kidney MDA when the ratio was 4:1, 2:1 or 1:1(P<0.05, P<0.01).The overall efficacy of Z values of LGT and JQC in the mass ratios including 4:1, 1:1, 1:2 and 1:4 was significantly higher than that in the ratio of 2:1(P<0.01).The half lethal dose(LD₅₀) of the LGT alone was 517 mg·kg^-1, while that of the LGT-JQC(2:1) ratio group increased to 889 mg·kg^-1 with an increase of 72%.The gray correlation coefficients of 12 chemical compositions with different characteristics produced before and after the compatibility and its overall efficacy Z value, the largest of which was triptolide(TP). Conclusion: LGT combined with JQC in the mass ratio of 4:1-1:4 attenuates LGT-induced subacute hepatotoxicity and nephrotoxicity, and the best ratio of such effect is 2:1.At the best ratio of 2:1, acute toxicity and subacute toxicity decrease by 72% and 138.5%, respectively.Triptolide is the most important chemical component that causes the attenuated effect of LGT combined with JQC.