祛湿涤浊汤对高尿酸血症大鼠尿酸转运蛋白的影响

Effect of Qushi-Dizhuo decoction on urate transporters in hyperuricemia rats

目的:探讨祛湿涤浊汤(QSDZ)对高尿酸血症大鼠尿酸转运体的影响。方法:60只健康雄性SD大鼠,随机分为空白对照组、模型组、别嘌呤醇组及祛湿涤浊汤低、中和高剂量组。除空白对照组外,其余各组采用腺嘌呤和氧嗪酸钾联合灌胃造模法制备高尿酸血症大鼠模型,各药物治疗组同时予以相应浓度制剂灌胃治疗,每日1次,连续用药28 d后处死大鼠。检测大鼠血清尿酸(UA)和肌酐(Cr)水平及黄嘌呤氧化酶(XOD)活性。取大鼠肾组织,HE染色观察肾组织形态学改变,Western blot法和real-time PCR法检测尿酸盐转运蛋白1(URAT1)、葡萄糖转运蛋白9(GLUT9)、有机阴离子转运蛋白1(OAT1)、ATP结合盒亚家族G成员2(ABCG2)和有机阳离子转运蛋白1(OCT1)的水平。结果:与空白对照组比较,模型组血清UA和Cr水平及XOD活性均显著升高(P<0.05),URAT1和GLUT9蛋白表达显著上调(P<0.05),OAT1,ABCG2和OCT1蛋白表达显著下调(P<0.05);与模型组比较,祛湿涤浊汤中、高剂量组的UA和Cr水平及XOD活性显著降低(P<0.05),URAT1和GLUT9蛋白表达显著下调(P<0.05),OAT1、ABCG2和OCT1蛋白水平显著上调(P<0.05)。URAT1、GLUT9、OAT1、ABCG2和OCT1 mRNA表达与其蛋白表达趋势一致。结论:祛湿涤浊汤可能是通过抑制XOD的活性及调节转运蛋白的表达来发挥抗高尿酸血症作用的。

AIM: To investigate the effects of Qushi-Dizhuo decoction(QSDZ) on the expression of uric acid transporters in rats with hyperuricemia. METHODS: Male Sprague-Dawley rats(n=60) were randomly divided into blank control group, model group, allopurinol group, and low-, middle-and high-dose QSDZ groups, with 10 rats in each. Except the blank control group, rats in the other groups were treated with adenine and potassium oxonate to prepare hyperuricemia rat model by intragastric administration once a day. Meanwhile, the rats in treatment groups were intragastric admi-nistrated with the corresponding preparation, after 28 days of continuous administration, the rats were sacrificed. Serum uric acid(UA) and creatinine(Cr) levels and xanthine oxidase(XOD) activity were measured. The morphological changes of renal tissues were observed by HE staining. The protein and mRNA expression of urate transporter1(URAT1), glucose transporter 9(GLUT9) and organic anion transporter 1(OAT1) were detected by Western blot and real-time PCR. ATP-binding cassette subfamily Gmember 2(ABCG2) and organic cation transporter 1(OCT1) were also determined. RESULTS: Compared with the blank control group, the content of UA and Cr and the activity of XOD were significantly increased(P<0.05), the URAT1 and GLUT9 protein levels were significantly up-regulated, and the OAT1, ABCG2 and OCT1 protein levels were significantly down-regulated in model group(P<0.05). Compared with model group, the levels of serum UA and Cr and actioity of DXD were significantly decreased in QSDZ middle,high-dose group(P<0.05). The protein levels of URAT1 and GLUT9 were decreased, while the protein levels of OAT1, ABCG2 and OCT1 were increased in middle-and high-dose groups compared with model group(P<0.05). The mRNA expression of URAT1, GLUT9, OAT1, ABCG2, OCT1 was consistent with its protein expression trend. CONCLUSION: QSDZ decoction may through inhibiting the activity of XOD and regulating the expression of transporter to show its anti-hyperuricemia effect.