目的 对《中国药典》收载的蒸制和酒炖2种炮制法所得熟地黄的化学成分进行比较研究。方法 整合基于HPLC （C₁₈）-PDA、HPLC （NH₂）-ELSD和高效凝胶渗透色谱（HPGPC）-ELSD的糖组学和基于UPLC-QTOF-MS/MS的代谢组学方法，对2种熟地黄的糖类组分（多糖、寡糖和游离单糖）和非糖小分子组分进行分析比较。结果 与蒸制地黄相比，酒炖地黄多糖相对分子质量范围更宽，较大相对分子质量多糖占比较高。2种熟地黄多糖均由甘露糖、半乳糖醛酸、葡萄糖、半乳糖和阿拉伯糖组成，但其物质的量比稍有不同（2.57：0.05：1.00：0.87：0.10 vs 2.07：0.07：1.00：1.05：0.17）。2种熟地黄均含有寡糖水苏糖、甘露三糖和蜜二糖，但酒炖地黄中水苏糖含量显著高于蒸制地黄（P<0.01）。2种熟地黄均含有游离单糖葡萄糖、果糖、鼠李糖、甘露糖、半乳糖和阿拉伯糖，但酒炖地黄中葡萄糖（P<0.01）、鼠李糖（P<0.05）和甘露糖（P<0.05）含量均显著低于蒸制地黄，而半乳糖含量显著高于蒸制地黄（P<0.05）。2种熟地黄中共筛选到29个差异性非糖小分子成分，主要为环烯醚萜苷类、苯乙醇苷类和呋喃醛衍生物。代表性成分定量分析表明，与蒸制地黄相比，酒炖地黄中梓醇、益母草苷和地黄苷D含量较高（P<0.01），密力特苷（P<0.05）和5-羟甲基糠醛（P<0.01）含量较低。结论 蒸制和酒炖地黄内在质量存在显著差异，这种内在质量差异是否会显著影响其药效仍有待深入研究。

Objective To compare the chemical profiles of Shudihuang (Rehmanniae Radix Praeparata, RRP) processed by steaming (RRP-S) and wine-stewing (RRP-W) documented in China Pharmacopeia. Methods HPLC-PDA, HPLC-ELSD and HPGPC-ELSD based glycomics and UPLC-QTOF-MS/MS based metabolomics were integrated to compare the glycome (polysaccharides, oligosaccharides and free monosaccharides) and metabolome (non-sugar small molecules) respectively in RRP-S and RRP-W. Results Compared with RRP-S, the molecular weight range of polysaccharides in RRP-W was broader, and the proportion of larger molecular weight polysaccharides was higher. Both the polysaccharides in RRP-S and RRP-W were composed of mannose, galacturonic acid, glucose, galactose and arabinose, but with different molar ratios (2.57:0.05:1.00:0.87:0.10 vs 2.07:0.07:1.00:1.05:0.17). Oligosaccharides stachyose, manninotriose and melibiose were detectable in both RRP-S and RRP-W with the content of stachyose significantly higher in RRP-W than that in RRP-S (P < 0.01). Free monosaccharides glucose, fructose, rhamnose, mannose, galactose and arabinose were detected in both RRP-S and RRP-W, with the contents of glucose (P < 0.01), rhamnose (P < 0.05) and mannose (P < 0.05) significantly lower, whereas galactose higher (P < 0.05) respectively, in RRP-W than that in RRP-S. A total of 29 non-sugar small molecules with significant abundance difference between RRP-W and RRP-S were identified or tentatively assigned, the chemical types of which belonged to iridoid glycosides, phenylethanoid glycosides and furfural derivative. The quantitative determination of the representative non-sugar small molecules showed that the contents of catalpol, leonuride and rehmannioside D were higher in RRP-W (P < 0.01), whereas melittoside (P < 0.05) and 5-hydroxymethylfurfural (5-HMF, P < 0.01) were lower in RRP-W, than that in RRP-S. Conclusion There is significant difference in intrinsic quality between RRP-S and RRP-W, and whether the quality variations could obviously affect the bioactivities of RRP-S and RRP-W deserves further investigation.

R283.6

国家自然科学基金项目（81872975）；国家自然科学基金项目（81603262）；江苏省中医药研究院自主科研项目（BM2018024-2019001）