虎桂药对组分配伍治疗高尿酸血症的作用及机制研究  

The Treatment and Mechanism Study on Hyperuricemia of Couplet Medicines Polydatin and Cinnamaldehyde

作　　者：叶玉珍 胡佳莉 龚梦鹃 刘伟欣 韩彬 胡旭光 邱玉琴 YE Yu-zhen;HU Jia-li;GONG Meng-juan;LIU Wei-xin;HAN Bin;HU Xu-guang;QIU Yu-qin(Traditional Chinese MedicineCollege,Guangdong Pharmaceutical University,Guangzhou 510006,China;Guangzhou Baiyunshan-Hutchison Whampoa Chinese Medicine Co.Ltd.,Guangzhou 510555,China;College of Pharmacy,Guangdong Pharmaceutical Uni-versity,Guangzhou510006,China)

机构地区：[1]广东药科大学中药学院,广东广州510006 [2]广州白云山和记黄埔中药有限公司,广东广州510555 [3]广东药科大学药科学院,广东广州510006

出　　处：《中药材》2020年第2期423-428,共6页Journal of Chinese Medicinal Materials

基　　金：国家自然科学基金面上项目(81173194);广东省联合培养研究生示范基地项目(GD20170803);2017年中央支持地方高校发展专项资金项目(2017121536)。

摘　　要：目的:探究虎杖苷和桂皮醛单体配伍对高尿酸血症大鼠的降尿酸作用及机制。方法:采用氧嗪酸钾(200 mg/kg)皮下注射,次黄嘌呤(50 mg/kg)和乙胺丁醇(250 mg/kg)灌胃建立高尿酸血症大鼠模型。造模5 d后,筛选造模成功的大鼠随机分为7组:正常对照组、模型组、别嘌醇(30 mg/kg)组、苯溴马隆(10 mg/kg)组及虎杖苷-桂皮醛低、中、高剂量(虎杖苷-桂皮醛:0.4 mg/kg+0.45 mg/kg、0.8 mg/kg+0.9 mg/kg、1.6 mg/kg+1.8 mg/kg)组。给药3 w后,分别检测血清中尿酸(SUA)、肌酐(Cr)和尿素氮(BUN)水平;qPCR测定肝脏黄嘌呤氧化酶(XOD)、腺苷脱氨酶(ADA)和肾脏葡萄糖转运子(GLUT9)、尿酸盐转运子(URAT1)的mRNA表达;Western Blot测定肝脏XOD和肾脏GLUT9、URAT1蛋白表达;肾脏组织行HE染色观察各组病理学变化。结果:与模型组比较,虎杖苷-桂皮醛中、高剂量组大鼠SUA水平显著降低,肝脏ADA、XOD和肾脏GLUT9、URAT1 mRNA及蛋白表达显著降低(P<0.05或P<0.01),肾组织病理学明显改善。虎杖苷-桂皮醛中剂量组血清BUN水平显著降低(P<0.05)。结论:虎杖苷和桂皮醛单体配伍具有显著的降尿酸作用,其作用机制可能与抑制大鼠肝脏中ADA、XOD mRNA和XOD蛋白及肾脏中GLUT9、URAT1 mRNA和蛋白表达有关。Objective:To investigate the effect of polydatin and cinnamaldehyde(PC)on uric acid lowering in rats with hyperuricemia and its mechanism.Methods:Hyperuricemia rats were established by hypodermic injection of Potassium Oxonate(200 mg/kg),intragastric administration of hypoxanthine(50 mg/kg)and ethambutol(250 mg/kg).After five days of modeling,the rats were randomly divided into seven groups,including blank group,model group,allopurinol group(30 mg/kg),benzbromaronegroup(10 mg/kg),PC low-,medium-and high-dose groups(polydatin+cinnamaldehyde:0.4 mg/kg+0.45 mg/kg,0.8 mg/kg+0.9 mg/kg and 1.6 mg/kg+1.8 mg/kg).Serum levels of uric acid(SUA),creatinine(Cr)and urea nitrogen(BUN)were measured after three weeks administration.The mRNA expressions of XOD,ADA,GLUT9 and URAT1 were determined by qPCR.The protein expressions of liver XOD,kidney GLUT9 and URAT1 were determined by Western blot.Kidney tissues were stained with HE to observe the pathological changes.Results:Compared with the model group,PC medium-and high-dose groups could significantly reduce the SUA level in rat serum,MRNA and protein expressions of ADA and XOD in liver and GLUT9 and URAT1 in kidney were significantly decreased(P<0.05 or P<0.01).Renal histopathology was significantly improved.The serum BUN level of the PC medium-dose group was significantly decreased(P<0.01).Conclusion:The combination of polygonin and cinnamaldehyde has significant uric acid lowering effect.The mechanism may be related to the inhibition of mRNA and protein expression of ADA and XOD in rat liver,XOD protein and GLUT9 and URAT1 in kidney.

关 键 词：高尿酸血症 虎杖苷 桂皮醛 黄嘌呤氧化酶 尿酸盐阴离子转运体1 果糖转运体9 

分 类 号：R285.5[医药卫生—中药学]