目的 结合TMT蛋白组学技术，探讨迷迭香酸抗大鼠高尿酸血症的作用机制。方法 将SD大鼠随机分为对照组、模型组、苯溴马隆组、迷迭香酸（50、100 mg/kg）组，除对照组给予蒸馏水外，其他各组大鼠均饮用10%果糖水建立高尿酸血症模型。连续给药4周后，检测血清尿酸水平，黄嘌呤氧化酶（XOD）与腺苷脱氨酶水平（ADA）活性，苏木素–伊红（HE）染色观察回肠组织病理变化，实时荧光定量PCR法（RT-qPCR）检测回肠组织尿酸转运体三磷酸腺苷结合转运蛋白G2（ABCG2）、葡萄糖转运体9（GLUT9）mRNA的表达，TMT蛋白组学检测大鼠回肠组织蛋白的表达。结果 与模型组比较，迷迭香酸可显著降低大鼠血清尿酸水平，降低XOD与ADA活性（P＜0.05、0.01、0.001），以及回肠组织内的GLUT9 mRNA的表达（P＜0.05）。TMT蛋白组测序共筛选出2 975个差异蛋白（log₂FC＞1.5，P＜0.05），通路分析显示迷迭香酸主要调节Th1/2/17细胞分化等通路。结论 迷迭香酸发挥抗大鼠高尿酸血症的作用机制可能与抑制ADA和XOD的活性，调节肠道GLUT9 mRNA表达和Th1/2/17细胞分化通路有关。

Objective To investigate the mechanism of rosmarinic acid against hyperuricemia in rats by TMT proteomics. Methods SD rats were randomly divided into control group, model group, benzbromarone group, and rosmarinic acid (50 and 100 mg/kg) group. Control group was given distilled water, and the other groups were given 10% fructose water to establish the model of hyperuricemia. After 4 weeks of continuous administration, the serum uric acid level, XOD and ADA activity were detected, and the pathological changes of ileum tissue were observed by HE staining. RT-qPCR was used to detect the gene expression of uric acid transporter ABCG2 and GLUT9 mRNA in the ileum tissue. TMT proteomics was used to detect the protein expression in the ileum tissue of rats. Results Compared with the model group, rosmarinic acid significantly reduced the serum uric acid level, improved XOD and ADA activities (P < 0.001, 0.05, 0.01), and improved the expression of GLUT9 mRNA in the ileum tissue (P < 0.05). A total of 2 975 differentially expressed proteins were screened by TMT proteome sequencing (log₂FC > 1.5, P < 0.05). Pathway analysis showed that rosmarinic acid mainly regulated Th1/2/17 cell differentiation and other pathways. Conclusion Mechanism of rosmarinic acid against hyperuricemia may be related to the inhibition of ADA and XOD activities, regulation of intestinal protein GLUT9 mRNA expression and Th1/2/17 cell differentiation pathway.

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国家自然科学基金青年科学基金项目资助项目（82204701）