淫羊藿苷抑制非小细胞肺癌生长的代谢组学研究  

Metabonomics study on effect of icariin on non-small cell lung cancer growth

作　　者：吕雅鑫 陈龙 蒋义鑫 常青祺 章丹丹 LYU Yaxin;CHEN Long;JIANG Yixin;CHANG Qingqi;ZHANG Dandan(Institute of Interdisciplinary Integrative Medicine Research,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Experiment Center for Science and Technology,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)

机构地区：[1]上海中医药大学交叉科学研究院,上海201203 [2]上海中医药大学科技实验中心,上海201203

出　　处：《上海中医药杂志》2021年第6期84-90,共7页Shanghai Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(81773946,81573673,81001666)。

摘　　要：目的利用液相色谱-质谱联用仪(LC-MS)考察淫羊藿苷干预非小细胞肺癌原位荷瘤裸鼠肿瘤生长中代谢组学的变化情况。方法建立非小细胞肺癌原位荷瘤裸鼠模型,随机分为模型组(即溶媒对照组)、淫羊藿苷给药组(予淫羊藿苷150 mg·kg-1·d-1),连续灌胃干预4周。小动物活体成像仪考察肺部肿瘤的生物发光值;HE染色考察肺组织变化;HPLC-LTQ-Orbitrap Elite液质联用技术检测血清中的代谢产物变化。结果淫羊藿苷给药组肿瘤生长显著抑制,较模型组肺部肿瘤的生物发光值显著降低(P<0.05),肺组织病变改善,而对体质量影响不大。模型组和淫羊藿苷给药组的血清代谢产物分布显著不同,通过正交偏最小二乘法-判别分析(OPLS-DA),遴选模型组与淫羊藿苷给药组比较变量权重(VIP)>1和组间统计值P<0.05的差异代谢物。与模型组比较,淫羊藿苷给药组有20种代谢物含量显著提高,包括D-色氨酸、4-乙烯基苯酚硫酸盐、去氢抗坏血酸、柠檬酸、N-乙酰亮氨酸、N-乙酰缬氨酸、硬脂酸、N-乙酰-L-色氨酸、γ-谷氨酰亮氨酸、高香草酸、抗坏血酸2-硫酸盐、吲哚、N-乙酰-L-蛋氨酸、溶血磷脂(LyP)、α-酮戊二酸、苹果酸、马尿酸、三聚乙醛、辛酰甘氨酸和γ-谷氨酰亮氨酸。其中显著变化的代谢产物富集途径主要为三羧酸循环、丙氨酸、天冬氨酸和谷氨酸的代谢、乙醛酸和二元酸酯的代谢以及丙酮酸的代谢。结论淫羊藿苷可能通过调控三羧酸循环、丙氨酸、天冬氨酸和谷氨酸的代谢、乙醛酸和二元酸酯、丙酮酸的代谢等途径,调控相关代谢产物水平,进而发挥抗非小细胞肺癌生长的作用。Objective To investigate the metabonomic changes of non-small cell lung cancer(NSCLC) tumor-bearing nude mice in vivo with icariin by liquid chromatography-mass spectrometry(LC-MS). Methods An orthotopic tumor-bearing mouse model was established and randomly divided into model group(vehicle control) and icariin administration group(150 mg·kg-1·d-1 of icariin). The drugs were given by intragastric administration continuously for 4 weeks. The bioluminescence value of lung tumor was examined by a living imaging system. The changes of lung tissue were examined by HE staining, and the changes of metabolites in serum were detected by HPLC-LTQ-Orbitrap Elite liquid chromatography-mass spectrometry. ResultsThe tumor growth was significantly inhibited in the icariin administration group, and the bioluminescence value of lung tumor in the icariin administration group was significantly lower than that in the model group(P<0.05). The pathological changes of lung tissue were improved, but had little effect on body mass. The levels of serum metabolites between the two groups showed different distributions. The differential metabolite was selected by VIP values >1 between the model group and the icariin administration group(P<0.05) by orthogonal partial least squares discriminant analysis(OPLS-DA). Compared with the model group, 20 metabolites significantly elevated in the icariin administration group, including D-tryptophan, 4-vinylphenol sulfate, dehydroascorbic acid, citric acid, N-acetyl-L-leucine, N-acetylvaline, stearic acid, N-acetyl-L-tryptophan, γ-glutamyl leucine, homovanillic acid, ascorbic acid 2-sulfate, indole, N-acetyl-L-methionine, lysolecithin(LyP), α-ketoglutaric acid, malic acid, hippuric acid, triacetaldehyde, octanoylglycine and γ-glutamyl leucine. These above metabolites were enriched in tricarboxylic acid cycle, alanine, aspartate and glutamate metabolism, glyoxylate and dicarboxylate metabolism, and pyruvate metabolism. Conclusion Icariin exerts anti-NSCLC effect by regulating tricarboxylic acid cyc

关 键 词：淫羊藿苷 非小细胞肺癌 裸鼠 代谢组学 三羧酸循环 

分 类 号：R285[医药卫生—中药学]