| 引用本文: | 沈倩,李贺,雷珊珊,江石平,李波,郑祥,颜美秋,吕圭源,陈素红.铁皮石斛四妙方对高尿酸血症模型大鼠的降尿酸作用及机制研究[J].中国现代应用药学,2019,36(2):157-163. |
| SHEN Qian,LI He,LEI Shanshan,JIANG Shiping,LI Bo,ZHENG Xiang,YAN Meiqiu,LYU Guiyuan,CHEN Suhong.Study on Anti-trioxypurine Effect and Mechanism of Dendrobium Candidum Simiao Prescription on Hyperuricemia Rats[J].Chin J Mod Appl Pharm(中国现代应用药学),2019,36(2):157-163. |
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| 铁皮石斛四妙方对高尿酸血症模型大鼠的降尿酸作用及机制研究 |
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沈倩1, 李贺1, 雷珊珊1, 江石平1, 李波1, 郑祥2, 颜美秋3, 吕圭源3, 陈素红1
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1.浙江工业大学, 杭州 310014;2.温州医科大学, 浙江 温州 325000;3.浙江中医药大学, 杭州 310053
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| 摘要: |
| 目的 研究铁皮石斛四妙方（Dendrobium candidum Simiao prescription，DSP）对腺嘌呤合乙胺丁醇致高尿酸血症模型大鼠的降尿酸作用，并从尿酸合成/排泄等途径探讨其作用机制。方法 将60只SD大鼠，♂，随机分为正常对照组、模型对照组、别嘌醇组、DSP高、中、低剂量组（1.2，2.4，4.8 g·kg-1）。采用腺嘌呤合乙胺丁醇灌胃制备高尿酸血症模型，每周测定血清尿酸（SUA）。给药第3周测定SUA、血肌酐（SCr）、血尿素氮（BUN）、尿液体积（UV）、尿尿酸（UUA）、尿肌酐（UCr），计算尿酸排泄指数。末次给药后，测定血清腺苷脱氨酶（ADA）、黄嘌呤氧化酶（XOD）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）的含量；测定肝脏鸟嘌呤脱氨酶（GDA）、次黄嘌呤-鸟嘌呤磷酸核糖转移酶（HGPRT）的含量；观察肾脏组织病理变化，免疫组化测定三磷酸腺苷结合盒转运蛋白2（ABCG2）、尿酸盐阴离子转运体1（URAT1）、葡萄糖转运体9（GLUT9）在大鼠肾脏的蛋白表达水平。结果 与模型对照组比，2.4 g·kg-1 DSP能显著降低高尿酸血症大鼠SUA水平（P<0.01），在第2周下降23%、第3周下降高达32%。机制研究表明2.4 g·kg-1 DSP能显著降低XOD、GDA含量（P<0.05或P<0.01），明显升高尿酸排泄指数（P<0.05），显著升高肾脏ABCG2蛋白表达水平（P<0.01），显著降低URAT1、GLUT9蛋白表达（P<0.01），降低血清炎症因子IL-6、TNF-α含量（P<0.05），可改善肾脏组织病理变化。结论 DSP可降低模型大鼠体内尿酸水平，可能与以下机制有关：通过降低XOD、GDA含量，减少尿酸生成；抑制URAT1、GLUT9蛋白表达，增加ABCG2表达水平，促进尿酸排泄；抑制炎症因子IL-6、TNF-α异常分泌，减少肾脏病变，从而发挥降尿酸作用。 |
| 关键词: 铁皮石斛四妙方 高尿酸血症 尿酸合成酶 尿酸转运体 炎症因子 |
| DOI：10.13748/j.cnki.issn1007-7693.2019.02.006 |
| 分类号:R285.5 |
| 基金项目:国家重点研发计划（2017YFC1702200）；国家自然科学基金项目（81673638，81874352）；国家自然科学基金青年基金项目（81703772） |
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| Study on Anti-trioxypurine Effect and Mechanism of Dendrobium Candidum Simiao Prescription on Hyperuricemia Rats |
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SHEN Qian1, LI He1, LEI Shanshan1, JIANG Shiping1, LI Bo1, ZHENG Xiang2, YAN Meiqiu3, LYU Guiyuan3, CHEN Suhong1
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1.Zhejiang University of Technology, Hangzhou 310014, China;2.Wenzhou Medical University, Wenzhou 325000, China;3.Zhejiang Chinese Medical University, Hangzhou 310053, China
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| Abstract: |
| OBJECTIVE To study the effect of Dendrobium candidum Simiao Prescription(DSP) on hyperuricemia rats induced by adenine and ethambutol and explore its mechanism. METHODS Sixty male SD rats were randomly divided into normal control group, model control group, allopurinol group, and DSP low, middle, high dose groups(1.2, 2.4, 4.8 g·kg-1). Hyperuricemia model was prepared by intragastric adenine and ethambutol, and serum urine uric acid (SUA) was measured weekly. At the third week of administration, SUA, serum creatinine(SCr), blood urea nitrogen(BUN), urine volume(UV), urine uric acid(UUA), and urine creatinine(UCr) were measured, and the uric acid excretion index was calculated. After the last administration, the contents of adenosine deaminase(ADA), xanthine oxidase(XOD), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α) in serum were measured. Besides, the content of guanine deaminase(GDA) and hypoxanthine-guanine phosphoribosyltransferase(HGPRT) in the liver were measured. The pathological changes of renal tissues were observed, and the protein expression levels of adenosine triphosphate binding cassette transporter 2(ABCG2), urate anion transporter 1(URAT1) and glucose transporter 9(GLUT9) in rat kidney were determined by immunohistochemistry. RESULTS Compared with the model control group, 2.4 g·kg-1 DSP significantly decreased the SUA level in hyperuricemia rats(P<0.01), which decreased by 23% in the second week and by 32% in the third week. The mechanism study showed that 2.4 g·kg-1 DSP could significantly reduce the content of XOD and GDA(P<0.05 or P<0.01), significantly increase the uric acid excretion index(P<0.05) and the expression of ABCG2 protein in the kidney(P<0.01), while significantly reduced the expression of URAT1, GLUT9(P<0.01) and decreased the content of inflammatory factors IL-6, TNF-α(P<0.05) in serum. In addition, it could improve the pathological changes in kidney tissue. CONCLUSION DSP can reduce the level of uric acid in model rats, which may be related to the following mechanisms:reduce uric acid production by decreasing the content of XOD and GDA, inhibiting the protein expression of URAT1, GLUT9, increasing the level of ABCG2, promoting uric acid excretion. Besides, it can inhibit the abnormal secretion of inflammatory factors IL-6 and TNF-α, reduce renal pathological changes. |
| Key words: Dendrobium candidum Simiao prescription hyperuricemia uric acid synthase uric acid transporter inflammatory factors |
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