目的 結(jié)合TMT蛋白組學(xué)技術(shù)，探討迷迭香酸抗大鼠高尿酸血癥的作用機(jī)制。方法 將SD大鼠隨機(jī)分為對(duì)照組、模型組、苯溴馬隆組、迷迭香酸（50、100 mg/kg）組，除對(duì)照組給予蒸餾水外，其他各組大鼠均飲用10%果糖水建立高尿酸血癥模型。連續(xù)給藥4周后，檢測(cè)血清尿酸水平，黃嘌呤氧化酶（XOD）與腺苷脫氨酶水平（ADA）活性，蘇木素–伊紅（HE）染色觀(guān)察回腸組織病理變化，實(shí)時(shí)熒光定量PCR法（RT-qPCR）檢測(cè)回腸組織尿酸轉(zhuǎn)運(yùn)體三磷酸腺苷結(jié)合轉(zhuǎn)運(yùn)蛋白G2（ABCG2）、葡萄糖轉(zhuǎn)運(yùn)體9（GLUT9）mRNA的表達(dá)，TMT蛋白組學(xué)檢測(cè)大鼠回腸組織蛋白的表達(dá)。結(jié)果 與模型組比較，迷迭香酸可顯著降低大鼠血清尿酸水平，降低XOD與ADA活性（P＜0.05、0.01、0.001），以及回腸組織內(nèi)的GLUT9 mRNA的表達(dá)（P＜0.05）。TMT蛋白組測(cè)序共篩選出2 975個(gè)差異蛋白（log₂FC＞1.5，P＜0.05），通路分析顯示迷迭香酸主要調(diào)節(jié)Th1/2/17細(xì)胞分化等通路。結(jié)論 迷迭香酸發(fā)揮抗大鼠高尿酸血癥的作用機(jī)制可能與抑制ADA和XOD的活性，調(diào)節(jié)腸道GLUT9 mRNA表達(dá)和Th1/2/17細(xì)胞分化通路有關(guān)。

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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國(guó)家自然科學(xué)基金青年科學(xué)基金項(xiàng)目資助項(xiàng)目（82204701）