目的 采用基于 1 H-NMR 的代谢组学方法分析脾虚湿热型难治性痛风患者的血清差异代谢物及代谢通 路。方法 选取 40 例脾虚湿热型难治性痛风急性发作患者作为痛风组，20 例健康体检者作为健康组。以血沉 及血清 C 反应蛋白 （CRP）、白细胞介素 6 （IL-6）、肿瘤坏死因子 α （TNF-α）、血清脂联素及肌酐水平作为观察 指标。采用 1 H-NMR 法进行血清代谢组学分析，所得数据进行主成分分析 （PCA） 及正交偏最小二乘法判别分析 （OPLS-DA），确定相对应的代谢产物并对差异代谢物进行潜在代谢通路分析。结果 与健康组比较，痛风组 患者的血沉及血清 CRP、IL-6、TNF-α 等各项炎症指标及细胞趋化因子水平显著升高（P＜0.01）；血清脂联 素水平显著降低（P＜0.01），血清肌酐水平显著升高（P＜0.01）。健康组与痛风组的血清代谢物的成分含量有 明显差异，共得到 44 种差异代谢物，涉及氨酰 tRNA 生物合成，缬氨酸、亮氨酸和异亮氨酸生物合成，丙氨 酸、天冬氨酸和谷氨酸代谢，糖酵解/糖异生，酮体的合成与降解，柠檬酸循环（TCA 循环），谷胱甘肽代谢及 甘油酯代谢等 12 条潜在代谢通路。结论 脾虚湿热型难治性痛风急性发作可能与线粒体能量代谢紊乱，导致 糖代谢、脂代谢及氨基酸代谢异常有关。

Objective To analyze the serum differential metabolites and metabolic pathways of patients with refractory gout of spleen deficiency and damp-heat type by metabolomics based on 1 H-NMR. Methods A total of 40 patients with refractory gout acute attack of spleen deficiency and damp-heat type were selected as gout group， and 20 healthy subjects were selected as healthy group. Erythrocyte sedimentation rate and serum C-reactive protein （CRP），interleukin-6（IL-6），tumor necrosis factor-α（TNF-α），serum adiponectin and creatinine levels were used as observation indicators. Serum metabolomics analysis was performed using 1 H-NMR method. The obtained data were subjected to principal component analysis（PCA）and orthogonal partial least squares discriminant analysis （OPLS-DA） to determine the corresponding metabolites and analyze the potential metabolic pathways of the differential metabolites. Results Compared with the healthy group，the erythrocyte sedimentation rate，serum CRP， IL-6，TNF- α and other inflammatory indicators and cell chemokine levels in the gout group were significantly increased （P＜0.01）； the serum adiponectin level was significantly decreased （P＜0.01）， and the serum creatinine level was significantly increased （P＜0.01）. There were significant differences in the content of serum metabolites between the healthy group and the gout group. A total of 44 differential metabolites were obtained， involving 12 potential metabolic pathways such as aminoacyl tRNA biosynthesis，valine，leucine and isoleucine biosynthesis，alanine，aspartic acid and glutamic acid metabolism，glycolysis/gluconeogenesis，ketone synthesis and degradation，citric acid cycle （TCA cycle），glutathione metabolism，glyceride metabolism. Conclusion Acute attacks of refractory gout with spleen deficiency and damp-heat type may be associated with disorders of mitochondrial energy metabolism，leading to abnormalities in glucose metabolism，lipid metabolism，and amino acid metabolism.

R2-03；R259

广东省中医药管理局科技专项资金项目 （20213020）