Department of Traditional Chinese Medicine, General Hospital of Guangzhou Military Command of PLA, Guangzhou 510010, China.
Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
J Ethnopharmacol. 2015 Feb 23;161:163-9. doi: 10.1016/j.jep.2014.12.001. Epub 2014 Dec 19.
Xie-Zhuo-Chu-Bi-Fang (XZCBF) is an empirical formula that was developed based on the principles of traditional Chinese medicine, for the therapeutic purpose of treating hyperuricemia. XZCBF has been clinically utilized in the Department of Traditional Chinese Medicine at General Hospital of Guangzhou Military Command of PLA for many years and has exhibited favorable efficacy. The aim of the study is to evaluate the effects of XZCBF on the expression of uric acid transporter 1 (URAT1) and miR-34a in hyperuricemic mice and to determine, the correlation between the two expression levels.
A hyperuricemic animal model was created by administering adenine and allantoxanic acid potassium salt to mice. The blood uric acid levels were measured in these model mice after treatment with XZCBF for 15 days. The potential targets of miR-34a were screened. The expression levels of miR-34a and URAT1 in the renal tissues collected from the model mice were determined by quantitative real-time polymerase chain reaction (qRT-PCR) analysis, and their correlation was further established by immunohistochemistry and in situ hybridization.
The uric acid levels in the model mice were significantly higher than those in the blank controls (P<0.05). These levels were significantly lower in the three groups receiving different doses of XZCBF (P<0.05), which was, in agreement with the downregulation of URAT1 and the upregulation of miR-34a in each group. The mRNA expression level of URAT1 was positively correlated with the concentration of uric acid but, negatively correlated with the expression level of miR-34a.
The ability of XZCBF to facilitate the excretion of uric acid and to lower its level in the model group was mediated by the upregulation of miR-34a and the inhibition of URAT1 mRNA expression, which suggests that XZCBF could be an option for the treatment of hyperuricemia in mice.
泄浊除痹方（XZCBF）是一种基于中医理论开发的经验方，用于治疗高尿酸血症。XZCBF 已在解放军广州军区总医院中医科临床应用多年，疗效良好。本研究旨在评价 XZCBF 对高尿酸血症小鼠尿酸转运蛋白 1（URAT1）和 miR-34a 表达的影响，并确定两者表达水平之间的相关性。
通过给予腺嘌呤和别嘌醇钾盐构建高尿酸血症动物模型，然后对这些模型小鼠给予 XZCBF 治疗 15 天，检测其血尿酸水平。筛选 miR-34a 的潜在靶标。采用实时定量聚合酶链反应（qRT-PCR）分析检测模型小鼠肾组织中 miR-34a 和 URAT1 的表达水平，并通过免疫组织化学和原位杂交进一步建立其相关性。
模型小鼠的血尿酸水平明显高于空白对照组（P<0.05）。XZCBF 三个剂量组的血尿酸水平均显著降低（P<0.05），与各组 URAT1 下调和 miR-34a 上调一致。URAT1 的 mRNA 表达水平与尿酸浓度呈正相关，与 miR-34a 的表达水平呈负相关。
XZCBF 促进尿酸排泄、降低模型组血尿酸水平的能力是通过上调 miR-34a 和抑制 URAT1mRNA 表达介导的，提示 XZCBF 可能是治疗小鼠高尿酸血症的一种选择。
