龙胆苦苷对果糖诱导小鼠高尿酸血症的作用

Effect of Gentiopicroside on Fructose-Induced Hyperuricemia in Mice

目的:研究龙胆苦苷对果糖诱导小鼠高尿酸血症的治疗作用。方法:昆明种小鼠连续饮用10%果糖溶液12周以制备高尿酸症小鼠模型,从第9周开始,别嘌呤醇组,龙胆苦苷高、中、低剂量组(80 mg/kg、40 mg/kg、20 mg/kg-)每天灌胃给药1次,共给药4周。末次给药后取血,检测血清谷丙转氨酶(GPT)、谷草转氨酶(GOT)、尿酸(UA)、肌酐(Cr)和血尿素氮(BUN)水平,苏木精-伊红(HE)染色观察肝、肾组织的变化;酶联免疫吸附试验法检测肾组织中超氧化物歧化酶(SOD),丙二醛(MDA),肿瘤坏死因子α(TNF-α)和白细胞介素-6(IL-6)水平,比色法和蛋白质免疫印迹法检测肝组织中黄嘌呤氧化酶(XOD)活性及蛋白表达水平。结果:与模型组比较,龙胆苦苷各给药组小鼠血清GPT、GOT、UA、Cra和BUN水平显著降低(P<0.01),肝、肾病理学变化有所改善;肾脏SOD水平显著升高(P<0.01),MDA、TNF-α和IL-6水平显著降低(P<0.01);同时肝脏XOD的活性及蛋白表达水平显著下调(P<0.01或P<0.05)。结论:龙胆苦苷通过降低XOD活性和表达,降低尿酸水平,进而减轻肾脏氧化应激和炎症水平,达到肾脏保护作用。

Objective:To investigate the effect of gentiopicroside on fructose-induced hyperuricemia in mice.Methods:The hyperuricmia KM mice were induced by feeding water containing 10%fructose for consecutive 12 weeks.During the period from 9th week to 12th week,mice from allopurinol group and gentiopicroside groups(80,40,20 mg/kg)received allopurinol and gentiopicroside,respectively by intragastric administration once a day for 4 weeks.The blood was collected after the last administration,to detect glutamic pyruvic transaminase(GPT),glutamic oxaloacetic transaminase(GOT),uric acid(UA),creatinine(Cr)and blood urea nitrogen(BUN)in serum.H&E staining was performed to observe the changes in liver and kidney tissues.Superoxide dismutase(SOD),malondialdehyde(MDA),tumor necrosis factor-α(TNF-α)and interleukin 6(IL-6)in kidney tissues were measured by enzyme-linked immunosorbent assay(ELISA),and the activity and expression of XOD in liver were tested by colorimetry and Western Blotting.Results:Compared with the model group,the mice in gentiopicroside groups showed a decrease in serum GPT,GOT,UA,Cr and BUN(P<0.01),with improvement in pathological changes of liver and kidney.The SOD in kidney were increased,whereas MDA,TNF-αand IL-6 were lowered(P<0.01).Moreover,gentiopicroside reduced the activity and protein expression of XOD in liver(P<0.01 or P<0.05).Conclusion:Gentiopicroside down-regulates UA in the fructose-induced hyperuricemia mice by modulating the activity and the expression of XOD,thereby alleviating oxidative stress,and inflammation and protecting the kidney.