樱桃果汁冻干粉通过调控尿酸转运蛋白减轻高尿酸性肾损伤

Alleviation of Hyperuricemic Renal Injury Using Freeze-dried Cherry Juice Powder to Regulate Uric Acid Transporters

摘要:

采用氧嗪酸钾连续腹腔注射7 d建立高尿酸血症（Hyperuricemia, HUA）小鼠模型，灌胃樱桃果汁冻干粉（Cherry Juice Freeze-Dried Powder, CJP）、苯溴马隆和别嘌呤醇干预HUA，试剂盒检测血清尿酸（Uric Acid，UA）、肌酐（Creatinine, Cr）、尿素氮（Blood Urea Nitrogen, BUN）；苏木素-伊红染色观察肝脏、肾脏病理改变；Western Blot和免疫组化检测小鼠肾脏尿酸转运蛋白的表达水平。探究CJP通过调控尿酸转运蛋白减轻高尿酸性肾损伤作用。结果显示：CJP高剂量组小鼠UA水平由191.99 μmol/L降低至113.12 μmol/L（P<0.01）但仍高于正常水平25%，而Cr水平由16.09 μmol/L降低至7.40 μmol/L（P<0.01），BUN水平由8.24 mmol/L降低至4.73 mmol/L（P<0.01）均达到正常水平。肾脏组织损伤改善明显。CJP下调了尿酸重吸收蛋白尿酸盐转运体1（Urate Transporter 1, URAT1）和葡萄糖转运蛋白9（Glucose Transporter 9, GLUT9），上调了尿酸分泌蛋白三磷酸腺苷结合盒转运体成员2（ATP-Binding Cassette Superfamily G Member 2, ABCG2）、阴离子转运蛋白-1（Anion Transporter 1, OAT1）、阴离子转运蛋白-3（Anion Transporter 1, OAT3）表达，对肝脏无明显毒性。因此，CJP可通过调控尿酸转运蛋白减轻高尿酸性肾损伤。该研究可为樱桃开发为防治尿酸性肾病的健康产品提供科学依据。

Abstract:

A hyperuricemia (HUA) mouse model was developed through intraperitoneal injection of potassium oxonate for 7 days to investigate the potential of CJP in alleviating hyperuricemic renal injury by regulating uric acid transporters. After intervention in the HUA model using freeze-dried cherry juice powder (CJP), benzbromarone, and allopurinol, serum uric acid (UA), creatinine (Cr), and blood urea nitrogen (BUN) were detected using commercially available kits. Pathological changes in the liver and kidney were determined using hematoxylin-eosin (HE) staining. Expression of uric acid transporters in mouse kidney was assessed using western blot and immunohistochemistry. The UA level in the high-dose CJP group decreased from 191.99 to 113.12 μmol/L (P<0.01), remaining 25% higher than the normal level, whereas the Cr level decreased from 16.09 to 7.40 μmol/L (P<0.01), and the BUN level decreased from 8.24 to 4.73 mmol/L (P<0.01). The latter two indicators reached normal levels, demonstrating a substantial alleviation of renal tissue injury. CJP downregulated the expression of two uric acid-reabsorbing proteins, urate transporter 1 and glucose transporter 9, while upregulating the protein expression of three uric acid-secreting proteins, ATP-binding cassette superfamily G member 2, anion transporter 1, and anion transporter 3, with no obvious liver toxicity. CJP thus alleviates hyperuricemic renal injury by regulating uric acid transporters. This study can serve as a scientific basis for the development of health products derived from cherry for preventing and treating hyperuricemic renal injury.