Study on Anti-trioxypurine Effect and Mechanism of Dendrobium Candidum Simiao Prescription on Hyperuricemia Rats

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.