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在氧嗪酸钾盐诱导小鼠产生高尿酸血症模型上,研究芒果苷促进尿酸排泄和肾功能改善以及调节相关肾脏转运体的作用。实验动物随机分为正常对照组、高尿酸血症模型对照组、芒果苷50、100和200mg·kg-1剂量组、别嘌醇5mg·kg-1剂量组。每天在灌胃给予氧嗪酸钾盐(250mg·kg-1)1h后灌胃给药,连续7天。分别测定血清尿酸、肌酐与尿素氮水平及尿液尿酸和肌酐水平。采用RT-PCR和Westernblotting方法分别测定动物肾脏转运体mRNA及蛋白表达水平。采用ELISA方法检测血清、尿液和肾脏尿调素(UMOD)含量。与模型对照组比较,芒果苷显著降低高尿酸血症小鼠血清尿酸、肌酐和尿素氮水平,提高24h尿液尿酸和肌酐排泄量以及尿酸排泄分数,具有促进肾脏尿酸排泄和保护肾功能作用。研究发现,芒果苷显著下调高尿酸血症小鼠肾脏尿酸盐重吸收转运体1(mURAT1)和葡萄糖转运体9(mGLUT9)mRNA和蛋白表达并上调肾脏有机阴离子转运体1(mOAT1)表达,提示芒果苷可能通过抑制肾脏尿酸重吸收和增加尿酸分泌而促进高尿酸血症小鼠尿酸排泄以降低血清尿酸水平。另外,芒果苷显著上调肾脏有机阳离子和肉毒碱转运体(mOCT1、mOCT2、mOCTN1和mOCTN2)表达水平、提高尿液mUMOD水平并降低血清和肾脏mUMOD水平,这些发现可能与其改善肾功能作用有关。
To study the effect of mangiferin on improving uric acid excretion and renal function and regulating the relevant renal transporter in a model of hyperuricemia induced by oxonic acid potassium salt in mice. The experimental animals were randomly divided into normal control group, hyperuricemia model control group, mangiferin 50,100 and 200mg · kg-1 dose group, allopurinol 5mg · kg-1 dose group. Oral administration of oxonic acid potassium salt (250mg · kg-1) was given intragastrically for 1h every day for 7 days. Serum uric acid, creatinine and urea nitrogen levels and urine uric acid and creatinine were measured. RT-PCR and Western blotting methods were used to determine the mRNA and protein expression levels of renal transporters. Serum, urine and renal urine uric acid (UMOD) levels were measured by ELISA. Compared with the model control group, mangiferin significantly reduced serum uric acid, creatinine and urea nitrogen levels in mice with hyperuricemia and increased uric acid and creatinine excretion and uric acid excretion scores in urine of 24 hours, promoting renal uric acid excretion and protecting renal function. The results showed that mangiferin significantly down-regulated the expression of mRNA and protein of renal urate salivary 1 and mGLUT9 and up-regulated the expression of mOAT1 in hyperuricemia mice, It is suggested that mangiferin may promote uric acid excretion and reduce serum uric acid level in hyperuricemic mice by inhibiting kidney uric acid reabsorption and increasing uric acid secretion. In addition, mangiferin significantly up-regulated the expression of renal organic cations and carnitine transporters (mOCT1, mOCT2, mOCTN1 and mOCTN2), increased urine mUMOD levels and decreased serum and renal mUMOD levels, which may be related to their improved renal function.