金雀花根水提物和乙醇提取物对小鼠高尿酸血症的影响

Effects of water extract and ethanol extract from the root of Caragana sinica on hyperuricemia in mice

目的探讨金雀花根水提物(WCS)和乙醇提取物(ECS)对小鼠高尿酸血症(HUA)的影响。方法将昆明种小鼠随机分为正常对照组、模型组、别嘌醇组(阳性对照,5 mg/kg)、苯溴马隆组(阳性对照,7.8 mg/kg)和WCS低、中、高剂量组(38、75、150 mg/kg)以及ECS低、中、高剂量组(50、100、200 mg/kg),每组10只。除正常对照组外,其余小鼠连续7 d腹腔注射氧嗪酸钾联合灌胃次黄嘌呤建立HUA模型。于建模第3天,各给药组小鼠灌胃相应药物,正常对照组和模型组灌胃等体积生理盐水,每日1次,连续5 d。称定给药期间小鼠的体质量;末次给药1 h后,计算肝、肾、脾的脏器指数,测定血清尿酸(SUA)、血尿素氮(BUN)、血肌酐(SCR)含量以及血清和肝组织中黄嘌呤氧化酶(XOD)活性;检测肝组织中XOD mRNA和蛋白的相对表达量以及肾组织中葡萄糖转运蛋白9(GLUT9)、尿酸转运蛋白1(URAT1)、有机阴离子转运蛋白1(OAT1)的相对表达量;观察肾组织的病理变化。结果各组小鼠肝脏指数和脾脏指数差异无统计学意义(P>0.05)。与正常对照组比较,除别嘌醇组外的各给药组小鼠的体质量和BUN、SCR含量差异无统计学意义(P>0.05);模型组和别嘌醇组小鼠的肾脏指数、SUA含量均显著升高(P<0.05);模型组小鼠血清和肝组织中XOD活性、肝组织中XOD mRNA和蛋白的相对表达量、肾组织中GLUT9和URAT1蛋白的相对表达量均显著升高(P<0.05),肾组织中OAT1蛋白的相对表达量显著降低(P<0.05)。与模型组比较,WCS和ECS各剂量组小鼠的肾脏指数均显著降低(P<0.05),肾组织病理损伤明显改善;各给药组小鼠的SUA含量、血清和肝组织中XOD活性、肝组织中XOD mRNA和蛋白的相对表达量、肾组织中URAT1蛋白的相对表达量均显著降低(P<0.05);苯溴马隆组和ECS高剂量组小鼠肾组织中GLUT9蛋白的相对表达量均显著降低(P<0.05);苯溴马隆组和WCS低、高剂量组以及ECS低剂量组小鼠肾组织中OAT1蛋白的相对表达量均显著升高(P<0.05)。结论WCS和ECS能够显著降低HUA模型小鼠SUA含量,改善其肾脏的病理状态,其作用机制可能与抑制XOD活性和尿酸重吸收、下调XOD蛋白和mRNA表达有关。

OBJECTIVE To investigate the effects of water extract(WCS)and ethanol extract(ECS)from the root of Caragana sinica on hyperuricemia(HUA)in mice.METHODS Kunming mice were randomly divided into normal control group,model group,allopurinol group(positive control,5 mg/kg),benzbromarone group(positive control,7.8 mg/kg),WCS low-dose,medium-dose and high-dose groups(38,75,150 mg/kg),ECS low-dose,medium-dose and high-dose groups(50,100,200 mg/kg),with 10 mice in each group.Except for the normal control group,the other mice were given potassium oxazinate intraperitoneally and hypoxanthine intragastrically for consecutive 7 d to establish HUA model.On the third day of modeling,mice in each administration group were given corresponding drugs intragastrically,and normal control group and model group were given equal volume of normal saline once a day for 5 consecutive days.The body weight of mice were weighted during administration;one hour after the last administration,the organ indexes of liver,kidney and spleen were calculated;the contents of serum uric acid(SUA),blood urea nitrogen(BUN)and serum creatinine(SCR);the activity of xanthine oxidase(XOD)in serum and liver tissue were determined.Relative mRNA and protein expressions of XOD in liver tissue,relative expressions of GLUT9,URAT1 and OAT1 in renal tissue were all detected;and the pathological changes of renal tissue were observed.RESULTS There were no significant differences in liver index and spleen index in each group(P>0.05).Compared with normal control group,except for allopurinol group,there were no significant differences in the body weight and the contents of BUN and SCR in mice of other administration groups(P>0.05);the renal index and SUA content of mice in the model group and allopurinol group were significantly increased(P<0.05);in the model group,the XOD activity in serum and liver tissue,the relative mRNA and protein expression of XOD in liver tissue,the relative expressions of GLUT9 and URAT1 protein in renal tissue were significantly increased(P<0.05),and the relative expression of OAT1 protein in renal tissue was significantly decreased(P<0.05).Compared with model group,renal indexes of mice were decreased significantly in WCS and ECS groups(P<0.05),and the pathological damage of renal tissue was significantly improved;SUA content,XOD activity in serum and liver tissue,the relative mRNA and protein expression of XOD in liver tissue,and the relative expression of URAT1 protein in renal tissue were decreased significantly in administration groups(P<0.05).The relative expression of GLUT9 protein in renal tissue of mice in benzbromarone group and ECS high-dose group decreased significantly(P<0.05);relative expression of OAT1 protein in renal tissue of mice in benzbromarone group,WCS low-dose and high-dose groups,ECS low-dose group were increased significantly(P<0.05).CONCLUSIONS WCS and ECS can significantly decrease the contents of SUA in HUA model mice,and improve pathological state of renal tissue,the mechanism of which may be associated with inhibiting XOD activity and uric acid reabsorption,and down-regulating protein and mRNA expression of XOD.