Effect of Tongfengning on Expression of Renal Urate Transporter in Hyperuricemia Rats / 中国实验方剂学杂志

ABSTRACT

Objective:Study on the mechanism of Tongfengning in promoting uric acid excretion from the perspective of urate transporter and mRNA in renal of hyperuricemia （HUA） model rats. Method:The 80 sprague-dawley rats were randomly divided into two groups， the blank group with 20 rats and the model group with 60 rats. Rats in model group were established as hyperuricemia （HUA） models by intraperitoneal injection of oxonic acid potassium salt （OAPS） and intragastric administration ethambutol hydrochloride （EMB） once a day for 21 days. After successful modeling， rats in the model group were divided into the model group， Tongfengning group and benzbromarone group， with 20 rats per group. Tongfengning solution （15.3 g·kg-1·d-1） was administered to the Tongfengning group by gavage feeding. Rats in benzbromarone group were administered 5.2 mg·kg-1·d-1 benzbromarone suspension， whereas those in the blank group and the model group were administered the equivalent amount of normal saline for 21 days. On days 14th and 21st following intervention， urine， blood， and kidney were collected from rats， serum uric acid （SUA） and urinary uric acid （UUA） levels， blood urea nitrogenand（BUN） and creatinine（CRE） levels and the expression of urate transporter proteins and their mRNAs of all rats were detected by enzyme-colorimetric method， urease method， sarcosine oxidase method， Western blot and Real-time quantitative PCR（Real-time PCR）， respectively. Result:On days 14th and 21th following intervention， compared with blank group， SUA， CRE and BUN levels， and urate transporter 1（URAT1），glucose transporter 9（GLUT9） expression increased（P<0.05，P<0.01）， whereas UUA level， and adenosine triphosphate-binding cassette transporter protein G2（ABCG2）， organic anion 1（OAT1）， organic anion 3（OAT3） expression decreased in the model group（P<0.05，P<0.01）. Compared with model group， SUA， CRE and BUN levels， and URAT1， GLUT9 expression decreased in Tongfengning group and the benzbromarone group（P<0.05）， whereas UUA level， and ABCG2， OAT1， OAT3 expression increased（P<0.05）. Creatinine and BUN levels decreased in the Tongfengning group（P<0.05，P<0.01）， with the trend much better than the benzbromarone group（P<0.05）. On day 21st， except for the BUN level did not change much compared with day 14th， all the rest indicators got improved obviously. Conclusion:Intraperitoneal injection of OAPS and intragastric administration of EMB can cause HUA models with renal dysfunction. Tongfengning reduced URAT1， GLUT9 mRNA and protein expression， and upregulated ABCG2， OAT1， OAT3 mRNA and protein expression in the rat kidney， which may be one of the mechanisms of promoting uric acid excretion. Tongfengning has a certain protective effect on renal function.