生物技术进展 ›› 2020, Vol. 10 ›› Issue (3): 256-264.DOI: 10.19586/j.2095-2341.2019.0084

• 研究论文 • 上一篇    下一篇

铁观音茶水提物对小鼠高尿酸血症的缓解作用

席圆圆§,徐宏彦§,刘霞,尹慧青,刘晓盼,王庆路,王清路*   

  1. 齐鲁医药学院, 山东省高校生物医学工程技术重点实验室, 山东 淄博 255300
  • 收稿日期:2019-08-26 出版日期:2020-05-25 发布日期:2019-10-18
  • 通讯作者: 王清路 E-mail:wql_zcq@126.com
  • 作者简介:§席圆圆和徐宏彦为共同第一作者,席圆圆 E-mail:3447407422@qq.com;徐宏彦 E-mail:634730288@qq.com
  • 基金资助:
    淄博市基因编辑与细胞应用平台项目(2018ZBXC010;2018ZBXC008)。

Alleviating Effect of Tieguanyin Tea Aqueous Extract on Hyperuricemia in Mice

XI Yuanyuan, XU Hongyan, LIU Xia, YIN Huiqing, LIU Xiaopan, WANG Qinglu, WANG Qinglu   

  1. Key Laboratory of Biomedical Engineering and Technology of Shandong High School, Qilu Medical University, Shandong Zibo 255300, China
  • Received:2019-08-26 Online:2020-05-25 Published:2019-10-18

摘要: 近年来,高尿酸血症(hyperuricemia,HUA)在人群中频发,危害性强,并发症多。为了探究日常饮品——半发酵茶铁观音茶水对于缓解HUA是否具有辅助作用,以小鼠为实验对象,采用氧嗪酸钾和次黄嘌呤联合法构建小鼠高尿酸血症模型,21只模型鼠随机分为模型组、铁观音茶水提物组、阳性药物组,7只非模型鼠作为对照。做不同处理2周后,取小鼠血清及肾、肝、小肠。观察各器官病理变化,从细胞层面鉴定铁观音茶水提物对高尿酸血症小鼠各脏器的影响;测定与HUA相关度较高的生化指标:血清尿酸(uric acid,UA)浓度、肝黄嘌呤氧化酶(xanthine oxidase,XOD)活力,以明确造模是否成功以及判断铁观音茶水提物对HUA是否具有缓解作用;利用qRT-PCR检测尿酸合成和排泄相关基因的mRNA表达水平,并利用Western blot检测肝XOD蛋白的表达水平,以从分子层面明确铁观音茶水提物对HUA的影响。病理切片显示,相比于阳性药物组,铁观音茶水提物组小鼠的肾和肝损害程度较轻;生化指标测定结果显示,铁观音茶水提物可降低血清尿酸水平,并且抑制XOD活性;从分子层面可以看出,铁观音茶水提物显著升高了尿酸重吸收转运体尿酸转运蛋白1(uric acid transporter 1,URAT1)和有机阴离子转运蛋白3(organic anion transporter 3,OAT3)的mRNA表达水平(P<0.05),显著降低了葡萄糖转运子9(glucose transporter 9,GLUT9)和有机阴离子转运蛋白1(organic anion transporter 1,OAT1)的表达水平(P<0.05)。虽然qRT-PCR和Western blot提示,XOD的mRNA和蛋白质的表达水平升高,但尿酸生成量却下降,推测可能是铁观音茶水提物中的某种成分使得无催化活性的XOD蛋白表达增加进而对XOD基因的转录表达造成一种正反馈。研究提示,铁观音茶水提物对小鼠高尿酸血症具有缓解作用,其缓解高尿酸血症的作用与抑制XOD活性、干预尿酸生成过程和刺激或抑制相关阴离子转运体mRNA的表达相关。

关键词: 铁观音茶水提物, 高尿酸血症, 有机阴离子转运体, 黄嘌呤氧化酶

Abstract: In recent years, hyperuricemia (HUA) occurs frequently in the population, with strong harmfulness and many complications. In order to explore whether semi-fermented  Tieguanyin tea, a common daily drink, has an auxiliary effect on alleviating HUA, mice were taken as experimental objects, and mice hyperuricemia models were established by the combined method of potassium oxazinate and hypoxanthine. Twenty-one model mice were randomly divided into model group, Tieguanyin tea aqueous extract group, positive drug group, and 7 non-model mice as controls. After 2 weeks of different treatments, mice serum, kidney, liver and small intestine were taken. The pathological changes of various organs were observed, so as to identify the effects of Tieguanyin tea aqueous extract on various organs of hyperuricemia mice from the cellular level. Biochemical indicators with high correlation with HUA were measured: concentration of serum uric acid (UA) and activity of xanthine oxidase (XOD) in liver to determine whether the model was successfully established and whether Tieguanyin tea aqueous extract had a mitigating effect on HUA. qRT-PCR was used to detect the mRNA expression level of genes related to uric acid synthesis and excretion, and Western blot was used to detect the expression level of liver XOD protein, so as to clarify the influence of Tieguanyin tea aqueous extract on HUA from the molecular level. Pathological sections showed that compared with the positive drug group, the mice in Tieguanyin tea aqueous extract group had less kidney and liver damage. Biochemical indexes showed that Tieguanyin tea aqueous extract could reduce serum uric acid level and inhibit XOD activity. From the molecular level, it could be seen that Tieguanyin tea aqueous extract significantly increased the mRNA expression levels of uric acid transporter 1 (URAT1) and organic anion transporter 3 (OAT3) (P<0.05), and the expression of glucose transporter 9 (GLUT9) and organic anion transporter 1 (OAT1) was significantly reduced (P<0.05). Although qRT-PCR and Western blot indicated that the expression level of XOD mRNA and protein increased, but the production of uric acid decreased, suggesting that a certain component in Tieguanyin tea aqueous extract may increase the expression of XOD protein without catalytic activity, thus causing a positive feedback to the transcription and expression of XOD gene. The research indicated that Tieguanyin tea aqueous extract had an alleviating effect on hyperuricemia in mice, and its alleviating effect was related to inhibiting XOD activity, intervening uric acid production process and stimulating or inhibiting mRNA expression of related anion transporters.

Key words: Tieguanyin tea aqueous extract, hyperuricemia, organic anion transporter, xanthine oxidase