目的:探讨肾脏尿酸盐转运子1(Urate Transporter 1,URAT1)、三磷酸腺苷结合盒转运蛋白G2(ATP-binding Cassette Superfamily G Member 2,ABCG2)、葡萄糖转运蛋白 9(Glucose Transporter 9,GLUT9)等尿酸转运蛋白在蠲痹历节清方降低血尿酸(Serum Uric Acid,SUA)中的机制。方法:将雄性SD大鼠随机分为空白组、模型组、苯溴马隆组(5 mg/kg)及蠲痹历节清方低、中、高剂量组(11,22,44 g/kg)。除空白组外,其余各组均建立高尿酸血症模型;苯溴马隆组和蠲痹历节清方组分别予相应浓度混悬液进行灌胃干预。最后收集大鼠腹主动脉血和双肾组织,采用全自动生化仪检测各组大鼠腹主动脉中血尿酸含量,采用实时荧光定量聚合酶链式反应(Real-time PCR)和蛋白免疫印迹法(Western Blot)检测各组大鼠肾脏中URAT1、GLUT9、ABCG2 mRNA和蛋白的表达。结果:与空白组相比,模型组血尿酸水平明显增加,差异有统计学意义(P<0。05);空白组与模型组血尿酸水平存在明显差异,提示造模成功。与空白组比较,模型组URAT1及GLUT9的mRNA和蛋白表达均显著升高,差异有统计学意义(P<0。05);ABCG2的mRNA和蛋白的表达则显著下降,差异有统计学意义(P<0。05)。与模型组比较,蠲痹历节清方各剂量组和苯溴马隆组URAT1及GLUT9的mRNA和蛋白表达均明显下降,差异有统计学意义(P<0。05);ABCG2的mRNA和蛋白的表达则显著升高,差异有统计学意义(P<0。05)。与蠲痹历节清方高剂量组比较,中、低剂量组URAT1及GLUT9的mRNA和蛋白表达均明显升高,差异有统计学意义(P<0。05);ABCG2的mRNA和蛋白的表达则明显下降,差异有统计学意义(P<0。05)。结论:蠲痹历节清方可通过抑制肾脏中URAT1、GLUT9 mRNA及蛋白表达,促进ABCG2的mRNA和蛋白的表达,来调节尿酸的分泌,减少尿酸的重吸收,增加尿酸的排泄,进而降低血尿酸水平,且随着剂量的升高,其降尿酸的作用逐渐增强。
Effect of Juanbilijieqing Recipe on the Partial Uric Acid Transporters in the Kidneys of Rat with Hyperuricemia
Objective:To study the mechanism of Juanbili-jieqing recipe in reducing serum uric acid(SUA)from the uric acid transporters such as renal URAT1(urate trans-porter 1),ABCG2(ATP-binding cassette superfamily G member 2)and GLUT9(glucose transporter 9).Methods:SD male rats were randomly divided into control group,mod-el group,benzbromarone group(5 mg/kg),low,medium and high dose groups(11,22,44 g/kg)of Juanbilijieqing recipe.Except for the blank group,hyperuricemia models were established in all other groups.Benzbromarone group and Juanbili-jieqing recipe group were given corresponding concentrations of suspension by intragastric administration to intervene.Finally,the blood of abdominal aorta and kidney tissue of rats were collected.The content of serum uric acid was detected by automatic biochemical instrument technology.The expressions of URAT1,GLUT9,ABCG2 mRNA and protein in the kidneys of rats were detected by real-time PCR and Western Blot.Results:Compared with the blank group,the SUA level in the model group increased significantly(P<0.05).There was a significant difference in SUA level between the blank group and the model group,indicating that the modeling was successful.Compared with the control group,the expression of URAT1,GLUT9 mRNA and protein increased significantly(P<0.05),while the expression of ABCG2 mRNA and protein decreased significantly in the model group(P<0.05).Compared with the model group,the expression of URAT1,GLUT9 mRNA and protein in each does of Juanbilijieqing recipe group and benzbromarone group decreased significantly(P<0.05),and the expression of ABCG2 mRNA and protein increased significantly(P<0.05).Compared with the Juanbilijieqing recipe high dose group,the expression of URAT1,GLUT9 mRNA and protein increased significantly(P<0.05),while the expression of ABCG2 mRNA and protein decreased significantly in the middle and low dose groups(P<0.05).Conclusion:Juanbilijieqing recipe can inhibit the expression of URAT1,GLUT9 mRNA and protein in kidney,promote the expression of ABCG2 mRNA and protein,reduce the secretion and reabsorption of uric acid,increase the excretion of uric acid,and then reduce the level of serum uric acid.And with the increase of dose,its effect of reducing uric acid gradually strengthened.
uric acidurate transporter 1(URAT1)ATP-binding cassette superfamily G member 2(ABCG2)glucose transporter 9(GLUT9)Juanbilijieqing recipe