从“化学成分谱-减毒作用谱-生物信息谱”关联分析整体评价雷公藤配伍金钱草的相杀减毒作用机制

Overall Evaluation on Mutual Detoxication Mechanism of Tripterygii Radix et Rhizoma and Lysimachiae Herba by Correlation Analysis of “Chemical Composition Spectrum-attenuation Spectrum-biological Information Spectrum”

目的:整体评价雷公藤(LGT)配伍金钱草(JQC)后在荷瘤状态下的相杀减毒作用机制。方法:以配伍前后12个差异特征成分为化学成分谱,以丙氨酸氨基转移酶(ALT),天门冬氨酸氨基转移酶(AST),肌酐(Cr)和尿素氮(BUN),肝丙二醛(MDA),肾MDA共6指标为减毒作用谱,以肝和肾的谷胱甘肽(GSH),谷胱甘肽-S-转移酶(GST),谷胱甘肽过氧化物酶(GPx),超氧化物歧化酶(SOD),过氧化氢酶(CAT),白细胞介素(IL)-10共12个生物指标作为生物信息谱,通过主成分分析(PCA)整体评价LGT-JQC在荷瘤S180和H22肿瘤状态下的相杀减毒作用及其机制,通过对"化学成分谱-减毒作用谱-生物信息谱"灰色关联分析(GCA)评价化学成分和生物指标对其相杀减毒作用的贡献大小。结果:与模型组比较,LGT单用后使S180和H22的减毒作用谱得分Z1值和Z3值均显著升高(P<0.01);与LGT单用组比较,LGT-JQC在质量配比为4∶1,2∶1,1∶1,1∶2,1∶4配伍时均能显著降低LGT引起的过高水平的Z1值和Z3值(P<0.01);LGT-JQC在质量比为4∶1,1∶1,1∶2,1∶4配伍时的Z1值和Z3值均明显高于质量比在2∶1时相应的Z1值和Z3值(P<0.01)。LGT能使S180和H22荷瘤状态下生物信息谱得分Z2值和Z4值均显著降低,配伍JQC可使Z2值和Z4值显著升高。对二者在S180和H22肿瘤状态下相杀减毒作用贡献最大的化学成分分别为3#和10#特征成分,贡献最大的生物指标分别为肾GPx和肾GSH。结论:LGT和JQC在质量比为4∶11∶4配伍时,对LGT所致的荷瘤S180和H22肿瘤状态下的毒性均有减毒作用,二者相杀减毒的最佳配比均为2∶1,减毒作用体现了中医"有故无殒"思想,其减毒作用机制涉及肝、肾的抗氧化损伤及抗炎症反应,其中尤以肾GPx(S180)和肾GSH(H22)对减毒作用机制的贡献最大。

Objective:To overall evaluate the mutual detoxication mechanism of Tripterygii Radix et Rhizoma(LGT)compatible with Lysimachiae Herba(JQC)in tumor-bearing state.Method:Twelve differentially characteristic components before and after compatibility were used as chemical composition spectrum,six indicators including serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),creatinine(Cr)and urea nitrogen(BUN),malondialdehyde(MDA)levels in the liver and kidney tissues were used as attenuation spectrum,and twelve biological indicators including glutathione(GSH),glutathione-S-transferase(GST),glutathione peroxidase(GPx),superoxide dismutase(SOD),catalase(CAT)and interleukin(IL)-10 in the liver and kidney were used as the biological information spectrum.Mutual detoxication mechanisms of LGT compatible with JQC in tumor-bearing state were overall evaluated by principal component analysis(PCA),and the contribution of chemical components and biological indicators to mutual detoxication was further evaluated by gray correlation analysis(GCA)of"chemical composition spectrum-attenuation spectrumbiological information spectrum".Result:Compared with the model group,the attenuation spectrum scores Z values of S180(Z1value)and H22(Z3value)increased significantly after LGT being used alone(P<0.01).Compared with LGT alone group,the compatibility groups of LGT and JQC significantly reduced excessive Z1value and Z3value caused by LGT when the ratio of LGT and JQC was 4∶1,2∶1,1∶1,1∶2 and 1∶4(P<0.01).The overall efficacy of Z values(Z1value and Z3value)of LGT-JQC in the mass ratios including 4∶1,1∶1,1∶2and 1∶4 was significantly higher than that in the ratio of 2∶1(P<0.01).LGT also caused a significant decrease in the Z values of the bioinformatics scores in the S180(Z2value)and H22(Z4value)tumor-bearing state,these two values were significantly increased after compatibility with JQC.The chemical components contributing the most to the attenuating effect of S180 and H22 in tumor-bearing state were 3#and 10#,respectively.The most important biological indicators were kidney GPx and renal GSH.Conclusion:LGT combined with JQC in the mass ratio of 4∶1-1∶4 can attenuate LGT-induced subacute toxicity in S180 and H22 tumor-bearing state,and the best ratio of such effect is 2∶1.The attenuating effect reflects the thought of"there is no reason why there is no meteorology".The mechanism of attenuating action involves antioxidative damage and anti-inflammatory reaction of the liver and kidney,especially the renal GPx(S180)and renal GSH(H22)as the greatest contribution to the detoxication mechanism.